Mice

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Mice

  • adolescent mouse
  • adult mouse
  • aged mouse
  • albino mouse
  • als mouse
  • altered mouse
  • anesthetized mouse
  • apcmin/+ mouse
  • apoe-deficient mouse
  • arthritic mouse
  • athymic mouse
  • athymic nude mouse
  • b6 mouse
  • b6c3f1 mouse
  • balb/cj mouse
  • bearing mouse
  • bigenic mouse
  • bxsb mouse
  • c mouse
  • c nude mouse
  • c3h mouse
  • c3h/hej mouse
  • c57 mouse
  • c57/bl6 mouse
  • c57bl mouse
  • c57bl/6 mouse
  • c57bl/6j male mouse
  • c57bl/6j mouse
  • c57bl/6n mouse
  • c57bl6 mouse
  • castrated mouse
  • cba mouse
  • cd-1 mouse
  • cd1 mouse
  • cell-deficient mouse
  • cf mouse
  • chimeric mouse
  • colitic mouse
  • combined immunodeficient mouse
  • congenic mouse
  • conscious mouse
  • control mouse
  • day-old mouse
  • dba/1 mouse
  • dba/1j mouse
  • dba/2 mouse
  • dba/2j mouse
  • ddy mouse
  • deer mouse
  • deficient mouse
  • developing mouse
  • diabetic mouse
  • diabetic nod mouse
  • donor mouse
  • double knockout mouse
  • double mutant mouse
  • double transgenic mouse
  • double-deficient mouse
  • double-knockout mouse
  • e-deficient mouse
  • eae mouse
  • el mouse
  • embryonic mouse
  • engineered mouse
  • experimental mouse
  • exposed mouse
  • f1 mouse
  • f2 mouse
  • feeding mouse
  • female c mouse
  • female c57bl/6 mouse
  • female c57bl/6j mouse
  • female icr mouse
  • female mouse
  • fetal mouse
  • fmr1 knockout mouse
  • fvb mouse
  • gene knockout mouse
  • gene-deficient mouse
  • genetically altered mouse
  • genetically modified mouse
  • germ-free mouse
  • gfp mouse
  • hairless mouse
  • hd mouse
  • healthy mouse
  • hen mouse
  • heterozygous mouse
  • homozygous mouse
  • house mouse
  • humanized mouse
  • icr mouse
  • immature mouse
  • immune-deficient mouse
  • immunized mouse
  • immunocompetent mouse
  • immunocompromised mouse
  • immunodeficient mouse
  • inbred mouse
  • individual mouse
  • infected mouse
  • intact mouse
  • irradiated mouse
  • j mouse
  • k/bxn mouse
  • kd mouse
  • knock-in mouse
  • knock-out mouse
  • knockin mouse
  • knockout mouse
  • ko mouse
  • laboratory mouse
  • lacz transgenic mouse
  • lean mouse
  • littermate control mouse
  • littermate mouse
  • lpr mouse
  • lupus mouse
  • lupus-prone mouse
  • male c mouse
  • male c57bl/6 mouse
  • male c57bl/6j mouse
  • male mouse
  • male nude mouse
  • mdx mouse
  • methods mouse
  • min mouse
  • model mouse
  • modified mouse
  • month-old mouse
  • moving mouse
  • mrl/lpr mouse
  • mutant mouse
  • naive mouse
  • naďve mouse
  • nc/nga mouse
  • neonatal mouse
  • neutropenic mouse
  • newborn mouse
  • nmri mouse
  • nod mouse
  • non-obese diabetic mouse
  • non-transgenic mouse
  • nontransgenic mouse
  • normal c mouse
  • normal c57bl/6 mouse
  • normal mouse
  • nu/nu mouse
  • nude mouse
  • null mouse
  • null mutant mouse
  • nzb mouse
  • ob mouse
  • obese mouse
  • old mouse
  • older mouse
  • oldfield mouse
  • ovariectomized mouse
  • ovx mouse
  • postnatal mouse
  • pregnant mouse
  • pten-deficient mouse
  • r6/2 mouse
  • receptor knockout mouse
  • receptor-deficient mouse
  • recipient mouse
  • recombinant inbred mouse
  • reeler mouse
  • reeler mutant mouse
  • reporter mouse
  • resistant mouse
  • samp10 mouse
  • scid mouse
  • scrapie-infected mouse
  • sensitized mouse
  • severe combined immunodeficient mouse
  • sham mouse
  • sjl mouse
  • skh-1 hairless mouse
  • spiny mouse
  • strain mouse
  • stressed mouse
  • suckling mouse
  • susceptible mouse
  • swiss albino mouse
  • swiss mouse
  • swiss webster mouse
  • swiss-webster mouse
  • syngeneic mouse
  • tramp mouse
  • transgenic mouse
  • treated mouse
  • tumor bearing mouse
  • tumor-bearing mouse
  • type mouse
  • uninfected mouse
  • untreated mouse
  • used mouse
  • used transgenic mouse
  • vaccinated mouse
  • vehicle-treated mouse
  • w/wv mouse
  • webster mouse
  • week-old mouse
  • white-footed mouse
  • wild mouse
  • wild type mouse
  • wild-type control mouse
  • wild-type mouse
  • wildtype mouse
  • wood mouse
  • wt mouse
  • young adult mouse
  • young mouse

  • Terms modified by Mice

  • mouse E cell
  • mouse astrocyte
  • mouse bone
  • mouse bone marrow
  • mouse bone marrow cell
  • mouse brain
  • mouse brain development
  • mouse calvaria
  • mouse cell
  • mouse central nervous system
  • mouse cerebellum
  • mouse chromosome
  • mouse colon
  • mouse cornea
  • mouse cortex
  • mouse decreased
  • mouse deer
  • mouse deficient
  • mouse dentate gyrus
  • mouse development
  • mouse egg
  • mouse embryo
  • mouse embryo development
  • mouse embryo fibroblast
  • mouse embryogenesi
  • mouse embryonic development
  • mouse embryonic fibroblast
  • mouse embryonic stem
  • mouse embryonic stem cell
  • mouse fetuse
  • mouse fibroblast
  • mouse fibroblast cell
  • mouse forebrain
  • mouse gene
  • mouse genetics
  • mouse genome
  • mouse heart
  • mouse hepatitis virus
  • mouse hepatocyte
  • mouse heterozygous
  • mouse hippocampal slice
  • mouse hippocampus
  • mouse homolog
  • mouse homologue
  • mouse homozygous
  • mouse hosts
  • mouse igg
  • mouse ileum
  • mouse inner ear
  • mouse intestine
  • mouse keratinocyte
  • mouse kidney
  • mouse lead
  • mouse lemur
  • mouse lense
  • mouse line
  • mouse liver
  • mouse liver tissue
  • mouse lung
  • mouse macrophage
  • mouse macrophage cell line
  • mouse melanoma
  • mouse model
  • mouse model system
  • mouse models
  • mouse monoclonal antibody
  • mouse muscle
  • mouse mutant
  • mouse neocortex
  • mouse neuromuscular junction
  • mouse null
  • mouse olfactory bulb
  • mouse olfactory system
  • mouse only
  • mouse oocyte
  • mouse ortholog
  • mouse osteoblast
  • mouse ovary
  • mouse peritoneal macrophage
  • mouse phenotype
  • mouse plasma
  • mouse platelet
  • mouse population
  • mouse prostate
  • mouse pup
  • mouse result
  • mouse retina
  • mouse sequence
  • mouse sera
  • mouse serum
  • mouse skeletal muscle
  • mouse skin
  • mouse soleus
  • mouse sperm
  • mouse spermatogenesis
  • mouse spermatozoa
  • mouse spinal cord
  • mouse spleen
  • mouse splenocyte
  • mouse strain
  • mouse striatum
  • mouse studies
  • mouse submandibular gland
  • mouse suprachiasmatic nucleus
  • mouse t cell
  • mouse testis
  • mouse tissue
  • mouse transgenic
  • mouse tumor
  • mouse urine
  • mouse uterus
  • mouse vas deferen
  • mouse xenograft
  • mouse xenograft model

  • Selected Abstracts


    Oral delivery of tumor-targeting Salmonella exhibits promising therapeutic efficacy and low toxicity

    CANCER SCIENCE, Issue 12 2009
    Guo Chen
    Tumor-targeting bacteria have been developed as powerful anticancer agents. Salmonella typhimurium VNP20009, a representative tumor-targeting strain, has been systemically administered as a single-agent therapy at doses of 1 × 106 to 3 × 106 colony-forming unit (cfu)/mouse, or in combination with other antitumor agents at doses of 1 × 104 to 2 × 105 cfu/mouse. Recently, we reported that oral delivery of VNP20009 at the dose of 1 × 109 cfu/mouse induced significant anticancer effects comparable to that induced by systemic administration of this strain at 1 × 104 cfu/mouse. To further address the efficacy and safety of oral administration of bacteria, here we performed a systemically comparative analysis of anticancer efficacy and toxicity of VNP20009 administered: (i) orally at a dose of 1 × 109 cfu/mouse (VNP9-oral); (ii) intraperitoneally at a dose of 1 × 104 cfu/mouse (VNP4-i.p.); or (iii) intraperitoneally at a dose of 1 × 106 cfu/mouse in tumor-free and tumor-bearing murine models. The results showed that VNP9-oral, similar to VNP4-i.p., induced significant tumor growth inhibition whereas VNP6-i.p. induced better anticancer effect in the B16F10 melanoma model. Among three treatments, VNP9-oral induced the mildest and reversible toxicity whereas VNP6-i.p. resulted in the most serious and irreversible toxicities when compared to other two treatments. Moreover, the combination of VNP9-oral with a low dose of chemotherapeutics produced comparable antitumor effects but displayed significantly reduced toxicity when compared to VNP6-i.p. The findings demonstrated that oral administration, as a novel avenue in the application of bacteria, is highly safe and effective. Moreover, the present preclinical study should facilitate the optimization of bacterial therapies with improved anticancer efficacy and reduced adverse effects in future clinical trials. (Cancer Sci 2009; 100: 2437,2443) [source]


    Induction of neuropeptides in skin innervating sensory neurons by stress and nerve growth factor as a possible reason for hair growth alteration

    EXPERIMENTAL DERMATOLOGY, Issue 9 2004
    A. Kuhlmei
    Recently, we introduced a mouse model launching experimental evidence for stress-induced hair growth inhibition (HGI), pointing to the existence of a brain-hair follicle axis (BFA). We suggested that nerve growth factor (NGF), besides neuropeptide substance P (SP), is a candidate mediator along the BFA. Published data further indicate that stress-related neuropeptides, e.g. calcitonin gene-related peptide (CGRP) and SP may be involved in HGI. SP and CGRP are synthesized in dorsal root ganglia (DRG) and released after axonal transport in the skin. Thus, aim of the present study was to investigate the effect of stress or subcutaneous injection of NGF, which mimics stress and regulates neuropeptide genes in sensory neurons, on the expression of SP and CGRP in DRG. Anagen was induced in C57BL/6 mice by depilation and retrograde tracing was employed on day 9 post-depilation (PD). On day 14 PD, mice were either exposed to sound stress (n = 4) injected subcutaneously with NGF (n = 4) or served as control (n = 4). On day 16 PD, DRG (mean of 30/mouse) were harvested and SP and CGRP in skin-specific sensory neurons, as identified by the tracer dye, were labelled by immunohistochemistry and counted. Stress exposure as well as NGF injection leads to a significant induction of SP and CGRP in retrograde-labelled neurons. This allows us to conclude that sensitive dermal nerve fibres are likely to originate from the presently identified neuropeptide-positive neurons. Peripheral activation of SP-expressing afferent nerve fibres via NGF-dependent pathways may cause neurogenic inflammation, eventually resulting in HGI. [source]


    Selection of an Escherichia coli O157:H7 bacteriophage for persistence in the circulatory system of mice infected experimentally

    CLINICAL MICROBIOLOGY AND INFECTION, Issue 3 2006
    R. Capparelli
    Abstract A bacteriophage lytic for Escherichia coli O157:H7 was isolated from bovine manure. Following in-vivo selection, the phage acquired the capacity to persist in the circulatory system of mice for at least 38 days. When mice were infected experimentally with E. coli O157:H7 (107 CFU/mouse), simultaneous injection of the mice with phage (108 PFU/mouse) cleared E. coli O157:H7 from the mice within 48 h. [source]


    Synergistic antiviral effect of a combination of mouse interferon-, and interferon-, on mouse hepatitis virus

    JOURNAL OF MEDICAL VIROLOGY, Issue 2 2003
    Uichiro Fuchizaki
    Abstract Although interferon (IFN)-, and IFN-, have been reported to exhibit a synergistic antiviral effect through the different signaling pathways in vitro, their therapeutic efficacy is not well defined in vivo. The current study was carried out to investigate the combined antiviral effect in a model of mouse hepatitis virus Type 2 (MHV-2) infection, in which fulminant hepatitis is developed. MHV-2 was injected intraperitoneally into 4-week-old ICR mice, IFN or the vehicle was administered intramuscularly for 5 days, and the antiviral effect was evaluated based on survival periods, liver histology, serum alanine transaminase (ALT) levels, and MHV-2 virus titers in the liver tissues. The animals in the group treated with a combination of IFN-, and IFN-, survived for longer periods than the groups treated with IFN-, alone and IFN-, alone (IFN-, 103 (IU/mouse)/-, 103 vs. IFN-, 103, P,<,0.005; IFN-, 103/-, 103 vs. IFN-, 103, P,<,0.001). This is consistent with the lower levels of hepatocellular necrosis and serum ALT and the decreased titers of MHV-2 virus in the liver tissues (48 hr, P,<,0.001; 72 hr, P,<,0.001). These findings indicate that a combination of IFN-, and IFN-, exhibits a synergistic antiviral effect on MHV-2 infection. The biology of MHV-2 is quite different from that of human hepatitis viruses; however, these results suggest the beneficial combined therapy of IFN-, and IFN-, for the treatment of human viral hepatitis. J. Med. Virol. 69:188,194, 2003. © 2003 Wiley-Liss, Inc. [source]


    RELATIVE CONTRIBUTION OF ADDITIVE, DOMINANCE, AND IMPRINTING EFFECTS TO PHENOTYPIC VARIATION IN BODY SIZE AND GROWTH BETWEEN DIVERGENT SELECTION LINES OF MICE

    EVOLUTION, Issue 5 2009
    Reinmar Hager
    Epigenetic effects attributed to genomic imprinting are increasingly recognized as an important source of variation in quantitative traits. However, little is known about their relative contribution to phenotypic variation compared to those of additive and dominance effects, and almost nothing about their role in phenotypic evolution. Here we address these questions by investigating the relative contribution of additive, dominance, and imprinting effects of quantitative trait loci (QTL) to variation in "early" and "late" body weight in an intercross of mice selected for divergent adult body weight. We identified 18 loci on 13 chromosomes; additive effects accounted for most of the phenotypic variation throughout development, and imprinting effects were always small. Genetic effects on early weight showed more dominance, less additive, and, surprisingly, less imprinting variation than that of late weight. The predominance of additivity of QTL effects on body weight follows the expectation that additive effects account for the evolutionary divergence between selection lines. We hypothesize that the appearance of more imprinting effects on late body weight may be a consequence of divergent selection on adult body weight, which may have indirectly selected for alleles showing partial imprinting effects due to their associated additive effects, highlighting a potential role of genomic imprinting in the response to selection. [source]


    FASTER FERTILIZATION RATE IN CONSPECIFIC VERSUS HETEROSPECIFIC MATINGS IN HOUSE MICE

    EVOLUTION, Issue 1 2009
    Matthew D. Dean
    Barriers to gene flow can arise at any stage in the reproductive sequence. Most studies of reproductive isolation focus on premating or postzygotic phenotypes, leaving the importance of differences in fertilization rate overlooked. Two closely related species of house mice, Mus domesticus and M. musculus, form a narrow hybrid zone in Europe, suggesting that one or more isolating factors operate in the face of ongoing gene flow. Here, we test for differences in fertilization rate using laboratory matings as well as in vitro sperm competition assays. In noncompetitive matings, we show that fertilization occurs significantly faster in conspecific versus heterospecific matings and that this difference arises after mating and before zygotes form. To further explore the mechanisms underlying this conspecific advantage, we used competitive in vitro assays to isolate gamete interactions. Surprisingly, we discovered that M. musculus sperm consistently outcompeted M. domesticus sperm regardless of which species donated ova. These results suggest that in vivo fertilization rate is mediated by interactions between sperm, the internal female environment, and/or contributions from male seminal fluid. We discuss the implications of faster conspecific fertilization in terms of reproductive isolation among these two naturally hybridizing species. [source]


    DIFFERENTIAL PATTERNS OF INTROGRESSION ACROSS THE X CHROMOSOME IN A HYBRID ZONE BETWEEN TWO SPECIES OF HOUSE MICE

    EVOLUTION, Issue 9 2004
    Bret A. Payseur
    Abstract A complete understanding of the speciation process requires the identification of genomic regions and genes that confer reproductive barriers between species. Empirical and theoretical research has revealed two important patterns in the evolution of reproductive isolation in animals: isolation typically arises as a result of disrupted epistatic interactions between multiple loci and these disruptions map disproportionately to the X chromosome. These patterns suggest that a targeted examination of natural gene flow between closely related species at X-linked markers with known positions would provide insight into the genetic basis of speciation. We take advantage of the existence of genomic data and a well-documented European zone of hybridization between two species of house mice, Mus domesticus and M. musculus, to conduct such a survey. We evaluate patterns of introgression across the hybrid zone for 13 diagnostic X-linked loci with known chromosomal positions using a maximum likelihood model. Interlocus comparisons clearly identify one locus with reduced introgression across the center of the hybrid zone, pinpointing a candidate region for reproductive isolation. Results also reveal one locus with high frequencies of M. domesticus alleles in populations on the M. musculus side of the zone, suggesting the possibility that positive selection may act to drive the spread of alleles from one species on to the genomic background of the other species. Finally, cline width and cline center are strongly positively correlated across the X chromosome, indicating that gene flow of the X chromosome may be asymmetrical. This study highlights the utility of natural populations of hybrids for mapping speciation genes and suggests that the middle of the X chromosome may be important for reproductive isolation between species of house mice. [source]


    International price competitiveness of Australia's MICE industry

    INTERNATIONAL JOURNAL OF TOURISM RESEARCH, Issue 2 2001
    Larry Dwyer
    Abstract A special-interest tourist market that holds out great promise for continued growth well into the next century is that of MICE (meetings, incentives, conventions, exhibitions). At the same time, changing prices in particular destinations relative to others are regarded as one of the most important economic influences on destination shares of total international tourism flows. The question arises as to the price competitiveness of major competing MICE destinations. Although earlier research has recognised that a destination's price competitiveness differs according to a visitor's country of origin there has been relatively little attention paid to tourism price competitiveness from the perspective of those having different motives for travel. This paper has four major aims: first, to provide a method by which price competitiveness of tourism by journey purpose can be estimated; second, to construct price competitiveness indices that measure, absolutely and relative to major competitors world-wide, the price competitiveness of Australia's MICE tourism industry; third, to compare Australia's price competitiveness as a MICE destination with its price competitiveness for total inbound tourism; fourth, to discuss the implications of the results for travel and tourism decision-makers in both the private and public sectors. Copyright © 2001 John Wiley & Sons, Ltd. [source]


    VIRULENCE LEVELS OF BIOFILM-GROWN LISTERIA MONOCYTOGENES LO28 ARE LOWER THAN THOSE OF PLANKTONIC CELLS IN AN ORAL INOCULATION TEST ON MICE

    JOURNAL OF FOOD SAFETY, Issue 1 2007
    ETIENNE ZUNDEL
    ABSTRACT The aim of this study was to produce Listeria monocytogenes biofilms suitable for virulence assays and to determine whether the released bacteria had the same virulence potential as their planktonic counterparts. Biofilms of Listeria monocytogenes LO28 strain, with or without Sphingomonas paucimobilis CCL10 strain, containing up to 7 log10 cfu/cm2 were produced in polypropylene syringes. The virulence of strain LO28 was analyzed in mice after intravenous, subcutaneous and oral inoculation. Its virulence level in binary cultures was not significantly different from that of monocultures. L. monocytogenes LO28 virulence in biofilms was lower than that of their planktonic counterparts after oral inoculation. Our results suggest that biofilms pose no greater health risk to the consumer than planktonic bacteria. [source]


    BONE MARROW TRANSFER FROM WILD-TYPE MICE REVERTS THE BENEFICIAL EFFECT OF GENETICALLY MEDIATED IMMUNE DEFICIENCY IN MYELIN MUTANTS

    JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2002
    M Maurer
    Inherited demyelinating neuropathies are chronically disabling human disorders caused by various genetic defects, including deletions, single site mutations, and duplications in the respective myelin genes. We have shown in a mouse model of one distinct hereditary demyelinating neuropathy (heterozygous PO-deficiency, PO±) that an additional null mutation in the recombination activating gene-1 (RAG-1--) leads to a substantially milder disorder, indicating a disease modifying role of T-lymphocytes. In the present study, we addressed the role of lymphocytes in the mouse model by reconstituting bone marrow of PO±/RAG-1-- mice with bone marrow from immunocompetent wild-type mice. We compared the pathology and nerve conduction in double mutant mice (PO±/RAG-1-- on a C57BL/6 background) with that in double mutants after receiving a bone marrow transplant. We found that the milder demyelination seen in the lymphocyte-deficient PO±/RAG-1-- mutants was reverted to the more severe pathology by reestablishing a competent immune system by bone marrow transfer. These data corroborate the concept that the immune system contributes substantially to the pathologic process in this mouse model and may open new avenues to ameliorate human hereditary neuropathies by exploiting immunosuppressive treatments. [source]


    LONG-TERM EXPOSURE TO EXTREMELY LOW-FREQUENCY MAGNETIC FIELDS IMPAIRS SPATIAL RECOGNITION MEMORY IN MICE

    CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2008
    Yu Fu
    SUMMARY 1In the present study, we investigated the short- and long-term effects of extremely low-frequency (ELF) magnetic fields on spatial recognition memory in mice by using a two-trial recognition Y-maze that is based on the innate tendency of rodents to explore novel environments. 2Mice were exposed to 25 or 50 Hz electromagnetic fields for either 7 (short term) or 25 days (long term) and then tested in the Y-maze. 3The results indicated that neither short- nor long-term exposure to magnetic fields affected the locomotor activity of mice in the Y-maze. However, long-term exposure to 50 Hz fields reduced recognition of the novel arm. 4Our findings suggest that ELF magnetic fields impair spatial recognition memory in the Y-maze depending on the field strength and/or duration of exposure. [source]


    OXIDATIVE STRESS IS AN IMPORTANT COMPONENT OF AIRWAY INFLAMMATION IN MICE EXPOSED TO CIGARETTE SMOKE OR LIPOPOLYSACCHARIDE

    CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2008
    Vincent Lagente
    SUMMARY 1It was proposed previously that oxidative stress is a main component of the inflammatory process in chronic obstructive pulmonary disease (COPD). Thus, in the present study, we investigated the inflammatory response in mice deficient for the p47phox subunit of NADPH oxidase (p47 KO) exposed to cigarette smoke (CS). 2Exposure of mice to CS elicited an increase in the number of macrophages and neutrophils and levels of interleukin (IL)-6, keratinocyte-derived chemokine (KC/CXCL1) and monocyte chemoattractant protein-1 (MCP1/CCL2) in bronchoalveolar lavage fluid (BALF), which were lower in p47 KO mice compared with control mice. In contrast, 24 h after lipopolysaccharide (LPS) exposure, the number of macrophages and neutrophils, as well as KC/CXCL1 levels, in BALF was significantly greater in p47 KO mice compared with control mice. 3The present study has shown that airway inflammation is decreased in p47 KO mice after exposure to CS, but not LPS, suggesting that oxidative stress is involved in the pathogenesis of airway inflammation associated with COPD. [source]


    MAXIMAL LACTATE STEADY STATE IN RUNNING MICE: EFFECT OF EXERCISE TRAINING

    CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2007
    Julio CB Ferreira
    SUMMARY 1Maximal lactate steady state (MLSS) corresponds to the highest blood lactate concentration (MLSSc) and workload (MLSSw) that can be maintained over time without continual blood lactate accumulation and is considered an important marker of endurance exercise capacity. The present study was undertaken to determine MLSSw and MLSSc in running mice. In addition, we provide an exercise training protocol for mice based on MLSSw. 2Maximal lactate steady state was determined by blood sampling during multiple sessions of constant-load exercise varying from 9 to 21 m/min in adult male C57BL/6J mice. The constant-load test lasted at least 21 min. The blood lactate concentration was analysed at rest and then at 7 min intervals during exercise. 3The MLSSw was found to be 15.1 ± 0.7 m/min and corresponded to 60 ± 2% of maximal speed achieved during the incremental exercise testing. Intra- and interobserver variability of MLSSc showed reproducible findings. Exercise training was performed at MLSSw over a period of 8 weeks for 1 h/day and 5 days/week. Exercise training led to resting bradycardia (21%) and increased running performance (28%). Of interest, the MLSSw of trained mice was significantly higher than that in sedentary littermates (19.0 ± 0.5 vs 14.2 ± 0.5 m/min; P = 0.05), whereas MLSSc remained unchanged (3.0 mmol/L). 4Altogether, we provide a valid and reliable protocol to improve endurance exercise capacity in mice performed at highest workload with predominant aerobic metabolism based on MLSS assessment. [source]


    EPLERENONE PREVENTS ADVERSE CARDIAC REMODELLING INDUCED BY PRESSURE OVERLOAD IN ATRIAL NATRIURETIC PEPTIDE-NULL MICE

    CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2006
    Veronica Franco
    SUMMARY 1Atrial natriuretic peptide (ANP)-null mice (Nppa -/- ) exhibit cardiac hypertrophy at baseline and adverse cardiac remodelling in response to transverse aortic constriction (TAC)-induced pressure overload stress. Previous studies have suggested that natriuretic peptides could potentially oppose mineralocorticoid signalling at several levels, including suppression of adrenal aldosterone production, inhibition of mineralocorticoid receptor (MR) activation or suppression of MR-mediated production of pro-inflammatory factors. Thus, we hypothesized that the MR blocker eplerenone would prevent the exaggerated left ventricular (LV) remodelling/fibrosis and dysfunction after TAC in Nppa -/- . 2In the present study, Nppa -/- and wild-type Nppa+/+ mice fed eplerenone- or vehicle (oatmeal)-supplemented chow since weaning were subjected to TAC or sham operation. The daily dose of eplerenone administered was approximately 200 mg/kg. At 1 week after TAC, LV size and function were evaluated by echocardiogram and LV cross-sections were stained with picrosirius red for collagen volume measurement. Total RNA was extracted from the LV for real-time polymerase chain reaction analysis of osteopontin. 3Eplerenone had no effect on baseline hypertrophy observed in sham-operated Nppa -/- compared with Nppa+/+ mice. Eplerenone attenuated the TAC-induced increase in LV weight in both genotypes and completely prevented LV dilation, systolic dysfunction and interstitial collagen deposition seen in Nppa -/- mice after TAC. However, serum aldosterone levels were lower in Nppa -/- compared with Nppa+/+ wild types. No interaction between eplerenone and genotype in osteopontin mRNA levels was observed. 4Eplerenone prevents adverse cardiac remodelling related to pressure overload in ANP-deficient mice, mainly due to an antifibrotic effect. The mechanism whereby ANP deficiency leads to excess hypertrophy, fibrosis and early failure following TAC is increased profibrotic signals resulting from excess or unopposed MR activation, rather than increased levels of aldosterone. [source]


    PERIPHERAL AND CENTRALLY MEDIATED EFFECTS OF INSULIN ON SMALL INTESTINAL TRANSIT IN HEALTHY MICE

    CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2006
    MK Peddyreddy
    SUMMARY 1Insulin is the drug of choice in the management of type 1 diabetes mellitus. Approximately 76% of diabetic patients suffer from gastrointestinal disorders. An important area of investigating the inherent effect of insulin on small intestinal transit (SIT) remains unexplored. Hence, the present study was planned to investigate the effects of insulin (2 × 10,6, 2 × 10,3 and 2 U/kg) on small intestinal transit following two different routes of administration in healthy animals. 2Insulin or vehicle was administered subcutaneously or intracerebroventricularly in eight groups of healthy, overnight-fasted mice. Blood glucose (BG) levels were measured 2 min before insulin administration and at the time coinciding with SIT determination. Small intestinal transit was determined 50 min after insulin administration using the charcoal meal method. 3Following subcutaneous administration, the lowest dose of insulin (2 × 10,6 U/kg) produced a significant acceleration in SIT without altering BG levels. However, the highest dose of insulin (2 U/kg) produced an acceleration of SIT that was associated with a significant fall in BG levels. 4Following intracerebroventricular administration, the lowest dose of insulin (2 × 10,6 U/kg) attenuated SIT, without producing any alteration in BG levels, but the highest dose (2 U/kg) mimicked the effects seen following subcutaneous administration. Peripherally administered insulin produced significant acceleration of SIT at lower doses (2 × 10,6 or 2 × 10,3 mU/kg) compared with centrally administered insulin at similar doses. However, at the highest dose of insulin (2 U/kg), both routes (s.c. and i.c.v.) produced acceleration of SIT. 5In the present study, peripherally and centrally administered insulin at 2 × 10,6 U/kg produced contrasting effects on SIT, without any hypoglycaemia. However, 2 U/kg insulin accelerated SIT similarly following both s.c. and i.c.v. administration that was associated with hypoglycaemia in healthy animals. [source]


    EFFECT OF NAPROXEN, A NON-SELECTIVE CYCLO-OXYGENASE INHIBITOR, ON PENTYLENETETRAZOL-INDUCED KINDLING IN MICE

    CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2005
    Ashish Dhir
    SUMMARY 1.,Epilepsy is one of the major neurological disorders of the brain, affecting approximately 0.5,1.0% of the population worldwide. Various neurotransmitter abnormalities, especially of GABA and glutamate, have been reported to play a key role in the pathophysiology of epilepsy. 2.,Cyclo-oxygenase (COX) is the rate-limiting enzyme in the production of prostaglandins and, as such, is a key target for many anti-inflammatory drugs. Cyclo-oxygenase has been reported to play a significant role in neurodegeneration. Recent studies have reported that COX plays a significant role in the pathophysiology of epilepsy. 3.,The aim of the present study was to explore the possible role of COX and the effect of COX inhibitors in epilepsy. 4.,Kindling is a chronic model of epilepsy. In the present study, kindling was induced in mice by chronic administration of a subconvulsive dose of pentylenetetrazole (PTZ; 40 mg/kg) on every other day for a period of 15 days. Naproxen was administered daily 45 min before PTZ or vehicle. The kindling score was recorded after PTZ administration. Seizure severity was measured according to a prevalidated scoring scale. Biochemical estimations were performed immediately after recording behavioural parameters on the 16th day of PTZ treatment. 5.,Chronic treatment with PTZ significantly induced kindling in mice. Pretreatment with the non-selective COX inhibitor naproxen (7 and 14 mg/kg, i.p.) showed significant protection against PTZ-induced kindling in mice. Biochemical analysis revealed that chronic treatment with PTZ significantly increased lipid peroxidation and nitrite levels (NO levels), but decreased reduced glutathione (GSH) levels in brain homogenates. 6.,In conclusion, the results of the present study strongly suggest that COX plays an important role in the pathophysiology of PTZ-induced kindling in mice and that COX inhibitors could be a useful neuroprotective strategy for the treatment of epilepsy. [source]


    EFFECTS OF MORPHINE ON METHOTREXATE DISPOSITION IN MICE

    CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2004
    Yuai Li
    SUMMARY 1.,Morphine has been shown to slow the renal excretion of other drugs. The present study in mice evaluated the effects of morphine on the disposition of methotrexate (MTX), an antimetabolite eliminated by the kidneys. 2.,Mice were injected with morphine (20 mg/kg) or saline s.c. After 30 min, 20,80 mg/kg MTX was injected i.v. Blood and urine samples were assayed for MTX by HPLC. 3.,Morphine reduced plasma clearance (CL) of MTX from 0.147 ± 0.015 to 0.061 ± 0.009 mL/min per g bodyweight (P < 0.01). The area under the plasma concentration,time curve (AUC0,,) was raised by morphine from 151 ± 18 to 369 ± 36 µg·mL per min (P < 0.01). Without morphine administration, 22,27% of an MTX dose was excreted into the urine in 30 min. The corresponding fractions excreted into the urine after morphine were reduced to 15,18% (P < 0.01). 4.,Plasma levels of MTX administered intravenously to mice are elevated by the concomitant administration of morphine, which reduces renal elimination of MTX. [source]


    Zebrafish as a model for long QT syndrome: the evidence and the means of manipulating zebrafish gene expression

    ACTA PHYSIOLOGICA, Issue 3 2010
    I. U. S. Leong
    Abstract Congenital long QT syndrome (LQT) is a group of cardiac disorders associated with the dysfunction of cardiac ion channels. It is characterized by prolongation of the QT-interval, episodes of syncope and even sudden death. Individuals may remain asymptomatic for most of their lives while others present with severe symptoms. This heterogeneity in phenotype makes diagnosis difficult with a greater emphasis on more targeted therapy. As a means of understanding the molecular mechanisms underlying LQT syndrome, evaluating the effect of modifier genes on disease severity as well as to test new therapies, the development of model systems remains an important research tool. Mice have predominantly been the animal model of choice for cardiac arrhythmia research, but there have been varying degrees of success in recapitulating the human symptoms; the mouse cardiac action potential (AP) and surface electrocardiograms exhibit major differences from those of the human heart. Against this background, the zebrafish is an emerging vertebrate disease modelling species that offers advantages in analysing LQT syndrome, not least because its cardiac AP much more closely resembles that of the human. This article highlights the use and potential of this species in LQT syndrome modelling, and as a platform for the in vivo assessment of putative disease-causing mutations in LQT genes, and of therapeutic interventions. [source]


    Effects of Coastal Lighting on Foraging Behaviorof Beach Mice

    CONSERVATION BIOLOGY, Issue 5 2004
    BRITTANY L. BIRD
    comportamiento de forrajeo; iluminación artificial; polución por luz; ratones de playa (Peromyscus polionotus leucocephalus) Abstract:,Introduction of artificial light into wildlife habitat represents a rapidly expanding form of human encroachment, particularly in coastal systems. Light pollution alters the behavior of sea turtles during nesting; therefore, long-wavelength lights,low-pressure sodium vapor and bug lights,that minimize impacts on turtles are required for beach lighting in Florida (U.S.A.). We investigated the effects of these two kinds of lights on the foraging behavior of Santa Rosa beach mice ( Peromyscus polionotus leucocephalus). We compared patch use and giving-up densities of mice for experimental food patches established along a gradient of artificial light in the field. Mice exploited fewer food patches near both types of artificial light than in areas with little light and harvested fewer seeds within patches near bug lights. Our results show that artificial light affects the behavior of terrestrial species in coastal areas and that light pollution deserves greater consideration in conservation planning. Resumen:,La introducción de luz artificial al hábitat de vida silvestre representa una forma de intrusión humana que se expande rápidamente, particularmente en sistemas costeros. Durante la anidación, la polución por luz altera el comportamiento de tortugas marinas; por tanto, para la iluminación de playas en Florida (E. U. A) se requieren luces de longitud de onda larga , luces de vapor de sodio de baja presión y contra insectos , que minimizan impactos sobre las tortugas. Investigamos los efectos de estos dos tipos de luces sobre el comportamiento de forrajeo de ratones de playa de Santa Rosa ( Peromyscus polionotus leucocephalus). Comparamos el uso de parches y las densidades de rendición de ratones en parches alimenticios experimentales establecidos a lo largo de un gradiente de luz artificial en el campo. Los ratones utilizaron menos parches de forrajeo cercanos a ambos tipos de luz artificial que en áreas con poca iluminación y cosecharon menos semillas en parches cercanos a luces contra insectos. Nuestros resultados muestran que la luz artificial afecta el comportamiento de especies terrestres en áreas costeras y que la polución por luz merece mayor consideración en la planificación de la conservación. [source]


    Cellular dynamics in the draining lymph nodes during sensitization and elicitation phases of contact hypersensitivity

    CONTACT DERMATITIS, Issue 5 2007
    Jeppe Madura Larsen
    Background:, The different role of various immunological effector cells in contact hypersensitivity (CHS) is receiving increased attention. During the past decade, the involvement of different cell types in CHS has been investigated by the use of antibody-induced depletion of specific subtypes of immunological cells and by studying knockout mice lacking one or more of these immunological cell populations. Objectives:, To develop a method for studying the collective cellular dynamics of immune cells in the draining lymph nodes during CHS in intact animals. Patients/Methods:, Mice were sensitized and/or challenged with 2,4-dinitrofluorobenzene or oxazolone. Using multi-parameter flow cytometry we determined the proliferation, activation state, and absolute number of helper T cells, cytotoxic T cells, B cells, and natural killer cells in the draining lymph nodes. Results:, The presented method can be applied to evaluate the effect of different contact allergens on various cell populations of the immune system. Conclusions:, Our study support recent findings that several cell types seem to be involved in CHS. [source]


    Enhancement of Viability of Fat Grafts in Nude Mice by Endothelial Progenitor Cells

    DERMATOLOGIC SURGERY, Issue 12 2006
    CHENGGANG YI MD
    BACKGROUND A recent discovery showed that endothelial progenitor cells (EPCs) could augment collateral vessel growth to ischemic tissues. OBJECTIVE The objective was to demonstrate the effects of EPCs on the vasculogenesis and survival of free transplanted fat tissues in nude mice. METHODS EPCs from human donors were cultured in vitro for 7 days. Human fat tissues were injected subcutaneously into the scalps of 20 6-week-old nude male mice. EPCs stained with CM-DiI were mixed with the transplanted fat tissues and injected into the mice. EBM-2 medium was used as control group. The animals were euthanized 15 weeks after the procedure. Graft volume were measured, and histologic evaluation was performed. The central part of fat tissues was histologically evaluated 15 weeks after the fat injection. RESULTS The survival volume of the experimental group was significantly greater than that of the control group (p< .05). Less cyst formation and fibrosis was obtained in the experimental group. Histologic evaluation of the central part of fat tissues 15 weeks after the fat injection showed that capillary densities increased markedly in the experimental group mice. CONCLUSION The results indicate that EPCs have the ability to enhance the survival and the quality of the transplanted fat tissues. [source]


    Mice with mutations in Mahogunin ring finger-1 (Mgrn1) exhibit abnormal patterning of the left,right axis

    DEVELOPMENTAL DYNAMICS, Issue 12 2006
    Christina D. Cota
    Abstract Mahogunin Ring Finger 1 (Mgrn1) encodes a RING-containing protein with ubiquitin ligase activity that has been implicated in pigment-type switching. In addition to having dark fur, mice lacking MGRN1 develop adult-onset spongy degeneration of the central nervous system and have reduced embryonic viability. Observation of complete situs inversus in a small proportion of adult Mgrn1 mutant mice suggested that embryonic lethality resulted from congenital heart defects due to defective establishment and/or maintenance of the left,right (LR) axis. Here we report that Mgrn1 is expressed in a pattern consistent with a role in LR patterning during early development and that many Mgrn1 mutant embryos show abnormal expression of asymmetrically expressed genes involved in LR patterning. A range of complex heart defects was observed in 20,25% of mid-to-late gestation Mgrn1 mutant embryos and another 20% were dead. This finding was consistent with 46,60% mortality of mutants by weaning age. Our results indicate that Mgrn1 acts early in the LR signaling cascade and is likely to provide new insight into this developmental process as Nodal expression was uncoupled from expression of other Nodal-responsive genes in Mgrn1 mutant embryos. Our work identifies a novel role for MGRN1 in embryonic patterning and suggests that the ubiquitination of MGRN1 target genes is essential for the proper establishment and/or maintenance of the LR axis. Developmental Dynamics 235:3438,3447, 2006. © 2006 Wiley-Liss, Inc. [source]


    Comment on "Endothelially Derived Nitric Oxide Affects the Severity of Early Acetaminophen-induced Hepatic Injury in Mice"

    ACADEMIC EMERGENCY MEDICINE, Issue 9 2006
    Kari Scantlebury MD
    No abstract is available for this article. [source]


    Endothelially Derived Nitric Oxide Affects the Severity of Early Acetaminophen-induced Hepatic Injury in Mice

    ACADEMIC EMERGENCY MEDICINE, Issue 5 2006
    Steven D. Salhanick MD
    Abstract Objectives: The precise mechanism of hepatocellular toxicity following acetaminophen (APAP) poisoning remains unclear. Nitric oxide is implicated in APAP toxicity as an inflammatory signaling molecule and as a precursor to the free radical peroxynitrate. The effects of inducible nitric oxide synthase (iNOS)-derived NO in APAP toxicity are known; however, the role of endothelial nitric oxide synthase (eNOS)-derived NO is unknown. The authors sought to evaluate the effect of eNOS-derived NO during APAP toxicity. Methods: C57BL6/J mice deficient in eNOS (eNOS KO) or iNOS (iNOS KO) and wild-type mice (WT) were treated with 300 mg/kg APAP. Alanine aminotransferase levels and plasma nitrate and nitrite levels were measured. Hypoxia inducible factor (HIF)-1, and Glucose Transporter 1 (Glut-1) levels were determined by Western blot. Results: Alanine aminotransferase levels were significantly elevated in all treated animals. Alanine aminotransferase levels were significantly lower in eNOS KO and iNOS KO than in treated WT animals. Plasma nitrate/nitrite levels were significantly higher in WT animals than in iNOS KO and eNOS KO animals. HIF-1, expression was increased in WT mice and decreased in iNOS KO mice. Glut-1 is a downstream, indirect marker of HIF function. Glut-1 expression was increased in WT and eNOS KO mice. Conclusions: Deficiency of either iNOS or eNOS results in decreased NO production and is associated with reduced hepatocellular injury following APAP poisoning. HIF-1, and Glut-1 levels are increased following APAP poisoning, implying that HIF-1, is functional during the pathogenic response to APAP poisoning. [source]


    Echocardiographic Evaluation of Ventricular Function in Mice

    ECHOCARDIOGRAPHY, Issue 1 2007
    Jeffrey N. Rottman M.D.
    Ventricular dysfunction remains a hallmark of most cardiac disease. The mouse has become an essential model system for cardiovascular biology, and echocardiography an established tool in the study of normal and genetically altered mice. This review describes the measurement of ventricular function, most often left ventricular function, by echocardiographic methods in mice. Technical limitations related to the small size and rapid heart rate in the mouse initially argued for the performance of echocardiography under anesthesia. More recently, higher frame rates and smaller probes operating at higher frequencies have facilitated imaging of conscious mice in some, but not all, experimental protocols and conditions. Ventricular function may be qualitatively and quantitatively evaluated under both conditions. Particular detail is provided for measurement under conscious conditions, and measurement under conscious and sedated or anesthestized conditions are contrasted. Normal values for echocardiographic indices for the common C57BL/6 strain are provided. Diastolic dysfunction is a critical pathophysiologic component of many disease states, and progress in the echocardiographic evaluation of diastolic function is discussed. Finally, echocardiography exists among several competing imaging technologies, and these alternatives are compared. [source]


    Infarct Size Assessment in Mice

    ECHOCARDIOGRAPHY, Issue 1 2007
    Marielle Scherrer-Crosbie M.D., Ph.D.
    Genetically modified mice are used extensively in models of ischemia reperfusion (I/R) and nonreperfused myocardial infarction (MI) to gain insights into pathways involved in these pathologies. Echocardiography is an ideal noninvasive tool to serially monitor the cardiac murine phenotype. The present review details the surgical aspects of I/R and MI models and the measurement of MI size by pathology techniques and the input of echocardiographic techniques including the extent of wall motion abnormality and of perfusion defects using myocardial contrast echocardiography in the assessment of murine area at risk and MI size. [source]


    Doppler Ultrasound in Mice

    ECHOCARDIOGRAPHY, Issue 1 2007
    Jörg Stypmann
    Color, power, spectral, and tissue Doppler have been applied to mice. Due to the noninvasive nature of the technique, serial intraindividual Doppler measurements of cardiovascular function are feasible in wild-type and genetically altered mice before and after microsurgical procedures or to follow age-related changes. Fifty-megahertz ultrasound biomicroscopy allows to record the first beats of the embryonic mouse heart at somite stage 5, and the first Doppler-flow signals can be recorded after the onset of intrauterine cardiovascular function at somite stage 7. Using 10- to 20-MHz ultrasound transducers in the mouse embryo, cardiac, and circulatory function can be studied as early as 7.5 days after postcoital mucous plug. Postnatal Doppler ultrasound examinations in mice are possible from birth to senescent age. Several strain-, age-, and gender-related differences of Doppler ultrasound findings have been reported in mice. Results of Doppler examinations are influenced by the experimental settings as stress testing or different forms of anesthesia. This review summarizes the present status of Doppler ultrasound examinations in mice and animal handling in the framework of a comprehensive phenotype characterization of cardiac contractile and circulatory function. [source]


    Echocardiographic Assessment of Left Ventricular Mass in Neonatal and Adult Mice: Accuracy of Different Echocardiographic Methods

    ECHOCARDIOGRAPHY, Issue 10 2006
    Alexander Ghanem M.D.
    Echocardiography is an established method to estimate left-ventricular mass (LVM) in mice. Accuracy is determined by cardiac size and morphology and influenced by mathematical models. We investigated accuracy of three common algorithms in three early developmental stages. High-resolution echocardiography was performed in 35 C57/BL6-mice. Therefore, two-dimensional-guided M-mode echocardiography and parasternal short- and long-axis views in B-mode were obtained. LVM was assessed in vivo applying Penn (P), Area Length (AL), and Truncated Ellipsoid (TE) algorithms and validated with histomorphometry. Regression analysis of all mice showed fair estimation of LVM assessed with M-mode-based Penn algorithm (y = 0.6*x , 0.12, r: 0.71). In contrast two-dimensional assessment of LVM revealed close linear relationship with histomorphometry (yAL= 1.21*x , 12.1, r: 0.88, yTE= 1.38*x , 2.88, r: 0.86). Bias was lowest for LVM-AL at diastole underestimating 3.2%. In concordance with the summarized data, LVM-P revealed lower regression coefficients and significant underestimation in all three subgroups. Small hearts (<50 mg, n = 12) correlated best with LVM-AL at systole. Hearts of adolescent (50,75 mg, n = 13) and adult (75,100 mg, n = 10) mice revealed close linear relationship with LVM-AL and LVM-TE at diastole. Echocardiographic assessment of LVM is feasible in hearts weighting less than 50 mg and can be estimated best in systole. Hearts weighting more than 50 mg are estimated most accurately by means of LVM-AL at diastole. [source]


    Pharmacokinetics, dose-range, and mutagenicity studies of methylphenidate hydrochloride in B6C3F1 mice,,

    ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 8 2008
    Mugimane G. Manjanatha
    Abstract Methylphenidate hydrochloride (MPH) is one of the most frequently prescribed pediatric drugs for the treatment of attention deficit hyperactivity disorder. In a recent study, increased hepatic adenomas were observed in B6C3F1 mice treated with MPH in their diet. To evaluate the reactive metabolite, ritalinic acid (RA) of MPH and its mode of action in mice, we conducted extensive investigations on the pharmacokinetics (PK) and genotoxicity of the drug in B6C3F1 mice. For the PK study, male B6C3F1 mice were gavaged once with 3 mg/kg body weight (BW) of MPH and groups of mice were sacrificed at various time points (0.25,24 hr) for serum analysis of MPH and RA concentrations. Groups of male B6C3F1 mice were fed diets containing 0, 250, 500, 1,000, 2,000, or 4,000 ppm of MPH for 28 days to determine the appropriate doses for 24-week transgenic mutation studies. Also, the micronucleus frequencies (MN-RETs and MN-NCEs), and the lymphocyte Hprt mutants were determined in peripheral blood and splenic lymphocytes, respectively. Mice fed 4,000 ppm of MPH lost significant BW compared to control mice (P < 0.01). There was a significant increase in the average liver weights whereas kidneys, seminal vesicle, testes, thymus, and urinary bladder weights of mice fed higher doses of MPH were significantly lower than the control group (P , 0.05). There was no significant increase in either the Hprt mutant frequency or the micronucleus frequency in the treated animals. These results indicated that although MPH induced liver hypertrophy in mice, no genotoxicity was observed. Environ. Mol. Mutagen., 2008. Published 2008 Wiley-Liss, Inc. [source]


    Studies of thioguanine-resistant lymphocytes induced by in vivo irradiation of mice

    ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 5 2008
    Irene M. Jones
    Abstract The frequency of Hprt -deficient lymphocytes in mice after in vivo , irradiation, has been found to vary as a function of time elapsed after exposure and irradiation dose. The frequency of mutant lymphocytes in spleen was determined using an in vitro, clonogenic assay for thioguanine-resistant T-lymphocytes. Mice were exposed to single doses of 0,400 cGy from cesium-137 or to eight daily doses of 50 cGy. The time to maximum-induced mutant frequency was 3 weeks. The dose response was strikingly curvilinear at 3,5 weeks after irradiation, but less precisely defined for 10,53 weeks after exposure, being fit by either linear or quadratic dependence. Three weeks after eight daily 50 cGy exposures, mutant frequency was elevated above controls and mice exposed to 50 cGy (which were not distinct from the nonirradiated controls), but only 17% in that of mice given a single 400 cGy fraction. This fractionation effect and the curvilinearity of the early dose,response curve suggested that saturation of repair increased the yield of mutations at higher acute doses. The decline of spleen mutant frequency in mice observed between 5 and 10 weeks after irradiation may reflect selection against some mutants. The marked variation of mutant frequency, as a function of time after irradiation and of dose rate, emphasize the need to evaluate these variables carefully and consistently in future studies. Environ. Mol. Mutagen., 2008. © 2008 Wiley-Liss, Inc. [source]