Home About us Contact
|
Home About us Contact | ||
|
|
||
Male Mice (male + mouse)
Kinds of Male Mice Selected AbstractsOsteoblast Deletion of Exon 3 of the Androgen Receptor Gene Results in Trabecular Bone Loss in Adult Male Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2007Amanda J Notini Abstract The mechanism of androgen action on bone was studied in male mice with the AR deleted in mature osteoblasts. These mice had decreased trabecular bone volume associated with a decrease in trabecular number, suggesting that androgens may act directly on osteoblasts to maintain trabecular bone. Introduction: Androgens modulate bone cell activity and are important for the maintenance of bone mass. However, the mechanisms by which they exert these actions on bone remain poorly defined. The aim of this study was to investigate the role of androgens acting through the classical androgen receptor (AR) signaling pathways (i.e., DNA-binding dependent pathways) in osteoblasts using male mice in which exon 3 of the AR gene was deleted specifically in mature osteoblasts. Materials and Methods: Mice with a floxed exon 3 of the AR gene were bred with Col 2.3-cre transgenic mice, in which Cre recombinase is expressed in mineralizing osteoblasts. The skeletal phenotype of mutant mice was assessed by histomorphometry and quantitative ,CT at 6, 12, and 32 weeks of age (n = 8 per group). Wildtype, hemizygous exon 3 floxed and hemizygous Col 2.3-cre male littermates were used as controls. Data were analyzed by one-way ANOVA and Tukey's posthoc test. Results: ,CT analysis of the fifth lumbar vertebral body showed that these mice had reduced trabecular bone volume (p < 0.05) at 32 weeks of age compared with controls. This was associated with a decrease in trabecular number (p < 0.01) at 12 and 32 weeks of age, suggesting increased bone resorption. These effects were accompanied by a reduction in connectivity density (p < 0.01) and an increase in trabecular separation (p < 0.01). A similar pattern of trabecular bone loss was observed in the distal femoral metaphysis at 32 weeks of age. Conclusions: These findings show that inactivation of the DNA binding,dependent functions of the AR, specifically in mature osteoblasts in male mice, results in increased bone resorption and decreased structural integrity of the bone, leading to a reduction in trabecular bone volume at 32 weeks of age. These data provide evidence of a role for androgens in the maintenance of trabecular bone volume directly through DNA binding,dependent actions of the AR in mature osteoblasts. [source] Androgen Receptor Expression in the Levator Ani Muscle of Male MiceJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2007J. A. Johansen The spinal nucleus of the bulbocavernosus (SNB) is a sexually dimorphic group of motoneurones that innervates the bulbocavernosus (BC) and levator ani (LA), skeletal muscles that attach to the base of the penis. In many species, including mice, rats and hamsters, the LA and BC have been found to be highly responsive to androgen and, in rats, these muscles mediate several effects of androgen on the SNB system. However, characterising the SNB system in mice is important because of the availability of genetic models in this species. In the present study, we examined AR expression in skeletal muscles of C57/BlJ6 adult male mice using immunoblotting and immunocytochemistry, comparing the BC/LA to the androgen-unresponsive extensor digitorum longus (EDL). We found similar differences in AR expression for these muscles in the mouse as previously reported for rats. In mice, the BC/LA contains more AR protein than does the EDL. At the cellular level, the LA contains a higher percentage of AR positive myonuclei and fibroblasts than does the EDL. Finally, AR expression is enriched at the neuromuscular junction of mouse LA fibres. The increased expression of AR in the LA compared to the EDL in both muscle fibres and fibroblasts indicates that each cell type may critically mediate androgen action on the SNB system in mice. [source] Oestrogen Receptor , is Essential for Female-Directed Chemo-Investigatory Behaviour but is not Required for the Pheromone-Induced Luteinizing Hormone Surge in Male MiceJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2000S. R. Wersinger The expression of normal masculine sexual behaviour requires testosterone. Testosterone can bind to androgen receptors, either in its native form, or after reduction to other androgen metabolites. In addition, testosterone can be aromatized to oestrogen, and bind to oestrogen receptor , and/or ,. Male copulatory behaviour is deficient in mice lacking functional oestrogen receptor , gene (ER,KO mice). We sought to determine which aspect(s) of masculine sexual behaviour is compromised in the ER,KOs. Specifically, we asked whether ER,KO males have reduced motivation and/or an inability to recognize oestrous females. We found significant differences between mice of different genotypes in the amount of chemo-investigatory behaviour displayed and in the target of their investigation. Wild-type males spent more time investigating ovariectomized, oestradiol-treated females, than either males, or ovariectomized females that had not received hormone priming. ER,KO males spent little time investigating any of the stimulus mice and showed no preferences. To test the hypothesis that this lack of chemo-investigatory behaviour is due to the inability of ER,KO males to detect and respond to female pheromones, we exposed males to chemosensory cues (soiled bedding) from females. Males resided in clean, or female-soiled, cage bedding for 60 min. Next, blood was collected and plasma luteinizing hormone (LH) assayed. We also assessed Fos-like immunoreactivity (Fos-ir) in several neural regions involved in processing chemosensory cues. Despite the fact that male ER,KOs spend little time engaged in chemo-investigation of females, their neuroendocrine responses to female-soiled bedding were similar to those seen in wild-type males. Our data suggest that the normal coupling between the neuroendocrine response to females and the generation of sexual behaviour is disrupted in ER,KO mice. Responses to female pheromones do not require ER,. However, normal male sexual performance requires the ER, gene. [source] Inflexible and Indifferent Alcohol Drinking in Male MiceALCOHOLISM, Issue 7 2010Heidi M. B. Lesscher Background:, Alcoholism is characterized by compulsive alcohol intake, but this critical feature of alcoholism is seldom captured in preclinical studies. Here, we evaluated whether alcohol-preferring C57BL/6J mice develop compulsive alcohol drinking patterns, using adulteration of the alcohol solution with quinine, in a limited access choice paradigm. We assessed 2 independent aspects of compulsive drinking: (i) inflexible alcohol intake by testing whether mice would drink bitter alcohol solutions if this was their only source of alcohol and (ii) indifferent drinking by comparing intake of aversive and nonaversive alcohol solutions. Methods:, Male C57BL/6J mice consumed alcohol for 2 or 8 consecutive weeks. The alcohol solution was then adulterated with graded quinine concentrations, and the effect on alcohol intake was determined. Results:, C57BL/6J mice rapidly developed compulsive alcohol drinking patterns. Adulteration of the alcohol solution with an aversive quinine concentration failed to reduce intake, indicative of inflexible drinking behavior, after only 2 weeks of alcohol experience, although quinine adulteration did suppress the acquisition of alcohol drinking in naïve mice. After 8 weeks of alcohol consumption, the mice also became indifferent to quinine. They consumed an aversive, quinine-containing alcohol solution, despite the simultaneous availability of an unadulterated alcohol solution. Prolonged alcohol ingestion did not alter the sensitivity to the bitter taste of quinine itself. Conclusion:, These findings demonstrate the staged occurrence in mice of 2 distinct behavioral characteristics of alcoholism, i.e., inflexible and indifferent alcohol drinking. [source] Only Male Mice Show Sensitization of Handling-Induced Convulsions Across Repeated Ethanol Withdrawal CyclesALCOHOLISM, Issue 3 2007L.M. Veatch Background: Alcohol abuse, especially when experienced in multiple cycles of chronic abuse and withdrawal, leads to a sensitization of central nervous system hyperexcitability that may culminate in overt expression of seizures. In spite of the growing prevalence of alcohol abuse and dependence in females shown in recent epidemiologic studies, evidence of sexual dimorphism in the expression of alcohol withdrawal-induced seizures and the development of seizure sensitization following multiple cycles of ethanol (EtOH) exposure and withdrawal has not been examined in either animal models or in clinical reports. Methods: Subjects in these experiments were male and female C3H/Hecr mice. The female mice were intact or ovariectomized, with ovariectomized mice receiving 17- , -estradiol or placebo pellets. All mice were exposed to 4 cycles of exposure to 16-hour EtOH vapor, separated by 8-hour withdrawal periods. During each 8-hour withdrawal, hourly assessment of seizure propensity was assessed as handling-induced convulsions. Additional assessments were taken up to 72 hours after the final EtOH withdrawal cycle. Results: Male and female mice showed similar seizure propensity during an initial withdrawal from chronic EtOH. Across subsequent withdrawal cycles, however, male mice exhibited a robust increase in seizure severity beginning with the third withdrawal cycle. In marked contrast, female mice failed to demonstrate sensitization of seizure severity. The lack of seizure sensitization following up to 4 cycles of alcohol exposure and withdrawal could not be explained by hormonal status (presence or absence of estrogen) or by sex differences in blood alcohol levels. Conclusions: Male and female mice exposed to the same number of cycles of EtOH withdrawal demonstrate differences in expression of seizures. Males show the typical sensitization of seizures, or kindling response, which has been reported clinically as well as in animal models, but females do not. The reason for the lack of seizure sensitization in female mice remains to be elucidated, but may be related to sex differences in alcohol effects on excitatory/inhibitory neurotransmission, rather than to hormonal or blood alcohol level differences. [source] ORIGINAL ARTICLE: Immunocontraceptive Effect of DNA Vaccine Targeting Fertilin , in Male MiceAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Zhongyi Sun Citation Sun Z, Jin F, Li Y, Zhang J. Immunocontraceptive effect of DNA vaccine targeting fertilin , in male mice. Am J Reprod Immunol 2010; 63: 282,290 Problem, In previous study, two eukaryotic expression plasmids pSG.SS.YL-F,.ECD and pSG.SS.C3d3.YL-F,.ECD were successfully constructed and transfected in HEK293 cells. Now, we want to evaluate the immunocontraceptive effect of these two DNA vaccines that target the extracellular domain (F,.ECD) of sperm antigen fertilin , subunit in Kunming male mice. Method of study, DNA vaccines pSG.SS.YL-F,.ECD and pSG.SS.C3d3.YL-F,.ECD were injected into Kunming male mice three times at 0, 4, and 8 weeks, respectively. An antifertility effect was observed. Serum antibody and cytokines were also detected. Results, Both vaccines significantly decreased both the pregnancy rate and the number of newborns. The serum levels of IL-2 and INF-, significantly decreased, whereas the levels of IL-4 and IL-10 significantly increased. Compared with pSG.SS.YL-F,.ECD, pSG.SS.C3d3.YL-F,.ECD was more effective in birth control, and its specific F, -IgG antibody titer in serum was significantly higher and longer. Conclusion, The results indicate that both pSG.SS.YL-F,.ECD and pSG.SS.C3d3.YL-F,.ECD DNA vaccines are effective in birth control of mice. The immunocontraceptive effect of F,.ECD DNA vaccine in male mice is improved with the addition of immuno-adjuvant C3d3. [source] Increase in Free Choice Oral Ethanol Self-Administration in Catechol- O -Methyltransferase Gene-Disrupted Male MiceBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2008Anne Tammimäki Solutions containing ethanol or cocaine, or tap water were available ad libitum from drinking burettes for 4 weeks. Catechol- O -methyltransferase-deficient male mice consumed significantly more ethanol than their wild-type male littermates. In contrast, female mice did not show genotype differences in the consumption of ethanol solutions. During the cocaine experiment, male mice developed either a side preference or an aversion that obscured cocaine consumption. This pattern of drinking was not dependent on Comt genotype. In female mice, Comt genotype was not associated with cocaine consumption. In conclusion, disruption of Comt gene influenced ethanol consumption in a gender-dependent manner in mice, supporting the hypothesis that low catechol- O -methyltransferase activity is one of the predisposing factors for high alcohol consumption in males. [source] Stress-Induced Analgesia and Morphine Responses Are Changed in Catechol- O -methyltransferase-Deficient Male MiceBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2008Oleg Kambur It is not clear how the effects of COMT are mediated and only few relevant animal studies have been performed. Here, we used old male Comt gene knock-out mice as an animal model to study the effects of COMT deficiency on nociception that was assessed by the hot plate and tail flick tests. Stress-induced analgesia was achieved by forced swim. Morphine antinociception was measured after 10 mg/kg of morphine subcutaneously. Morphine tolerance was produced with subcutaneous morphine pellets and withdrawal provoked with subcutaneous naloxone. In the hot plate test, morphine-induced antinociception was significantly greater in the COMT knock-out mice, compared to the wild-type mice. This may be due to increased availability of opioid receptors as suggested by previous human studies. In the tail flick test, opioid-mediated stress-induced analgesia was absent and morphine-induced analgesia was decreased in COMT knock-out mice. In the hot plate test, stress-induced analgesia developed to all mice regardless of the COMT genotype. There were no differences between the genotypes in the baseline nociceptive thresholds, morphine tolerance and withdrawal. Our findings show, for the first time, the importance of COMT activity in stress- and morphine-induced analgesia in mice. COMT activity seems to take part in the modulation of nociception not only in the brain, as suggested earlier, but also at the spinal/peripheral level. [source] Gravitational unloading inhibits the regenerative potential of atrophied soleus muscle in miceACTA PHYSIOLOGICA, Issue 3 2009Y. Matsuba Abstract Aim:, The present study was performed to investigate the influence of unloading on the regeneration of atrophied and injured skeletal muscle. Methods:, Male mice (C57BL/6J), aged 8 weeks, were used. Cardiotoxin (CTX) was injected into soleus muscles bilaterally. Gravitational unloading on soleus muscle was performed by hind limb suspension for 2 weeks before and additionally 6 weeks after CTX injection in one group. Soleus muscles in the remaining groups were loaded keeping the mice in the cages and were dissected 14, 28 and 42 days after the injection. Results:, Recovery of the wet weight and protein content of soleus in the CTX-injected group was inhibited by unloading. Increase in satellite cell number, induced by CTX injection and loading, was also inhibited by unloading. Disappearance of infiltration of mononucleated cells into the necrotic area was also delayed. This phenomenon suggests that regeneration, which is indicated by the appearance of fibres with central nuclei, was inhibited by unloading. Conclusion:, Results suggested that loading plays an important role in the activation of the regenerating potential of injured skeletal muscle. [source] Further studies on knockout mice lacking a functional dynein heavy chain (MDHC7).CYTOSKELETON, Issue 2 2005Abstract Male mice had been previously generated in which the inner dynein arm heavy chain 7 gene (MDHC7) was disrupted. MDHC7,/, animals show asthenozoospermia and are sterile. Very few of their spermatozoa can achieve forward progression, but for those that can, we add here the information (1) that the three-dimensional aspects of their movement are normal; (2) that their maximum velocity is less than that of wild-type controls; and (3) that they are entirely unable to penetrate media of raised viscosity (25,4,000 cP). However, the large majority of the spermatozoa can achieve only a low amplitude vibration. In these sperm we find, using electron microscopy, that the outer dense fibres retain attachments to the inner surface of the mitochondria. Such attachments are present in normal epididymal mouse spermatozoa but are broken down as soon as the sperm become motile on release from the epididymis. The attachments are presumed to be essential during midpiece development and, afterwards, to require a threshold level of force to loosen them and so permit the sliding displacements necessary for normal bending. We presume that the disruption of the inner dynein arm heavy chain gene, MDHC7, means that there is insufficient force to overcome the attachments, for all but a few spermatozoa. Cell Motil. Cytoskeleton 61:74,82, 2005. © 2005 Wiley-Liss, Inc. [source] Effect of Pectin Enhancement on Plasma Quercetin and Fecal Flora in Rutin-Supplemented MiceJOURNAL OF FOOD SCIENCE, Issue 9 2007M. Tamura ABSTRACT:, Few reports have considered the effects of dietary fiber on plasma quercetin and the intestinal flora. We investigated the effects of pectin on the plasma and fecal flora of mice fed a diet supplemented with the quercetin glycoside rutin. Male mice were randomly divided into 2 groups, which were fed a pectin,rutin (PR) or cellulose,rutin (CR) diet for 14 d. Plasma quercetin and isorhamnetin metabolites were measured by high-performance liquid chromatography. Feces were immediately processed with bacteriological procedures. The fecal flora was investigated. Plasma quercetin and isorhamnetin concentrations were significantly higher in the PR diet group, as was the plasma isorhamnetin/quercetin ratio. The composition of the intestinal flora differed between the 2 dietary groups. The total number of fecal bacteria was significantly larger in the PR group, in which most types of bacteria were more abundant, with the exceptions of bifidobacteria, fusiform-shaped bacteria, and staphylococci. The lower gut seemed to be the major absorption site for rutin. Pectin might thus enhance the bioavailability of quercetin from rutin by altering the metabolic activity of the intestinal flora and/or gut physiological function. [source] Withdrawal Severity After Chronic Intermittent Ethanol in Inbred Mouse StrainsALCOHOLISM, Issue 9 2010Pamela Metten Background:, To study withdrawal, ethanol is usually administered chronically without interruption. However, interest has recurred in models of episodic exposure. Increasing evidence suggests that chronic intermittent exposure to ethanol leads to a sensitization effect in both withdrawal severity and ethanol consumption. The goal of the present study was to examine mouse inbred strain differences in withdrawal severity following chronic intermittent exposure using the handling-induced convulsion as the behavioral endpoint. We also sought to compare the withdrawal responses of inbred strains across acute, chronic continuous, and chronic intermittent exposure regimens. Methods:, Male mice from 15 standard inbred strains were exposed to ethanol vapor for 16 hours each day for 3 days and removed to an air chamber during the intervening 8 hours. Mice in the control groups were handled the same, except that they were exposed only to air. Daily blood ethanol concentrations were averaged for each mouse to estimate total dose of ethanol experienced. Results:, Across strains, mice had an average daily blood ethanol concentration (BEC) of 1.45 ± 0.02 mg/ml and we restricted the range of this value to 1.00,2.00 mg/ml. To evaluate strain differences, we divided data into two dose groups based on BEC, low dose (1.29 ± 0.1 mg/ml) and high dose (1.71 ± 0.02 mg/ml). After the third inhalation exposure, ethanol-exposed and air-exposed groups were tested hourly for handling-induced convulsions for 10 hour and at hour 24 and 25. Strains differed markedly in the severity of withdrawal (after subtraction of air control values) in both dose groups. Conclusion:, The chronic intermittent exposure paradigm is sufficient to elicit differential withdrawal responses across nearly all strains. Data from the high-dose groups correlated well with withdrawal data derived from prior acute (single high dose) and chronic continuous (for 72 hours) ethanol withdrawal studies, supporting the influence of common genes on all three responses. [source] Estrogen configures sexual dimorphism in the preoptic area of C57BL/6J and ddN strains of miceTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 17 2010Chitose Orikasa Abstract Immunohistochemistry using a calbindin D28k antibody revealed a marked sex difference in neuronal distribution in the central portion of the medial preoptic area in C57BL/6J and ddN strains of mice when the animals were sacrificed on D65 (D1 = the day of birth). Male mice had a distinct ellipsoidal cell aggregate, whereas females lacked such a structure. This sex difference was not observed in Nissl-stained sections. Co-localization of calbindin D28k and the neuron-specific nuclear protein NeuN confrmed that the cells in the aggregate were neurons. The aggregates were larger in males than in females in both strains. When observed on D65, males orchidectomized on D1 had smaller aggregates. However, daily injections of 2 ,g estradiol benzoate through D1,D5 as well as a single injection of 100 ,g testosterone propionate on D1 enlarged the aggregates in females, but a single injection of 100 ,g dihydrotestosterone on D1 had no effect on the female phenotype. Similar endocrine manipulations had no effects in adult animals of both sexes. Thus, the calbindin-immunoreactive cell aggregates in the preoptic area of C57BL/6J and ddN mice are homologous to the sexually dimorphic nucleus of the rat preoptic area in terms of the morphology and sex steroid-dependent organization. J. Comp. Neurol. 518:3618,3629, 2010. © 2010 Wiley-Liss, Inc. [source] Peripheral olfactory sensitivity in rodents after treatment with docetaxel,THE LARYNGOSCOPE, Issue 4 2010Frédéric Faure MD Abstract Objectives/Hypothesis: Clinical studies have documented that cytotoxic chemotherapy is often associated with body weight loss and decreased enjoyment of food. Besides taste, olfaction plays a role in food intake. We assessed whether systemic chemotherapeutic cancer treatment compromises olfactory function in rats and mice treated with docetaxel (Taxotere; Sanofi-Aventis, Paris, France). Study Design: Randomized, controlled trials on mice and rats. Methods: Male mice received a single and male rats either a single, two, or three docetaxel administrations. Olfactory function was tested by means of electroolfactograms (EOGs) from the chemosensory epithelium of the nasal septum and the endoturbinates. We evaluated and compared the magnitude of EOG responses evoked by different odorants recorded at different time points after treatment. Results: In both animal species, docetaxel administration reduced body weight gain, thus evidencing the general toxic effect of the drug. In both animal species, the olfactory mucosa remained responsive to stimulation of odorants during the whole course of experiment, but treatment revealed regional differences of docetaxel susceptibility and induced marked transitory electrophysiological changes. In mice and rats a significant transitory decrease in EOG response magnitude occurred after a single administration. Unexpectedly, in rats we also observed an increase of the olfactory response following the second administration of the drug. Conclusions: Docetaxel exerts a neurotoxic effect on olfactory epithelia of rodents at doses similar to human doses, thus inducing transitory functional alterations. Although moderate, they are consistent with the hypothesis of a dysfunction of olfactory function. Further experiments are needed to elucidate the origin of the electrophysiological effects and their impact on the olfactory perception. Laryngoscope, 2010 [source] Effects of oyster extract on the reproductive function of zinc-deficient mice: Bioavailability of zinc contained in oyster extractCONGENITAL ANOMALIES, Issue 4 2003Yoshikazu Matsuda ABSTRACT Zinc is a vital nutrient in the normal reproductive function and embryonic development of mammals, and it is well known that oyster extract contains significant amounts of zinc. The effects of oyster extract on reproductive function, such as embryonic development, serum levels of zinc and sperm maturation were examined in zinc-deficient mice. Zinc deficiency in dams during pregnancy induced a decrease in the successful pregnancy rate, maternal weight gain, the number of live fetuses and fetal body weight. Zinc deficiency for 12 weeks in male mice induced a decrease in body weight, testis weight and sperm count in the epididymis. However, reproductive failure, embryonic defects and decreased sperm motility in zinc-deficient mice were improved by supplementation with oyster extract. Some nutrients contained in oyster extract, such as taurine and glycogen, may be related to the recovery of reproductive function. There were significantly lower serum concentrations of zinc in dams fed a zinc-deficient diet However, the serum zinc concentration was normal in the oyster extract-supplemented group. No difference in the concentration of serum zinc was observed between the oyster extract- and zinc carbonate-supplemented groups. From these findings, it is suggested that oyster extract is a useful supplement that can prevent reproductive defects from zinc deficiency, and the bioavailability of zinc may be identical to zinc carbonate. [source] Lowered albumin extravasation rate in heart but not in other organs in ,3-integrin-deficient miceACTA PHYSIOLOGICA, Issue 4 2009Ø. S. Svendsen Abstract Aim:, The vascular protein permeability is dependent on the integrity of the vascular wall. The heart capillaries in male mice lacking ,3 integrins have an immature phenotype. Previously, we have demonstrated a role for ,v,3 integrins in control of interstitial fluid pressure (Pif) and thereby in the fluid flux during inflammation. We wanted to explore a possible role for ,v,3 integrins in controlling capillary protein permeability during control situation and inflammation. Methods:, We performed double-tracer and microdialysis experiments on ,3-integrin-deficient mice and wild type control mice. We also measured blood pressure and heart rate in the two mice strains. Results:, We found reduced albumin extravasation (during 25 min) in the heart capillaries (0.053 ± 0.003 vs. 0.087 ± 0.009 mL g,1 dw, P < 0.05), and an increased cardiac mass/body weight (5.3 × 10,3 ± 0.3 × 10,3 vs. 3.8 × 10,3 ± 0.1 × 10,3, P < 0.01) in the ,3-integrin-deficient mice (n = 6) compared with the controls (n = 6). Heart rate and blood pressure were the same in mice with and without ,3-integrins. No difference in permeability was found in other tissues studied, or under local inflammation. Conclusion:, These results show a function for the ,v,3 integrin in the regulation of protein permeability, selective for the heart capillaries. [source] Enhancement of Viability of Fat Grafts in Nude Mice by Endothelial Progenitor CellsDERMATOLOGIC SURGERY, Issue 12 2006CHENGGANG 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] Postnatal stress in mice: Does "stressing" the mother have the same effect as "stressing" the pups?DEVELOPMENTAL PSYCHOBIOLOGY, Issue 4 2004A. Moles Abstract Short- and long-term effects of brief maternal separation, maternal exposure to novel male odor, and standard rearing were compared in NMRI mice. The first condition consisted of 15 min of daily exposure of pups to clean bedding (CB), and the second condition consisted of 15 min of mothers' exposure to the odor of strange males (SM), for 14 days after birth starting from postnatal Day 1. Thus, both conditions entailed the same period of maternal separation. A control mother,offspring group was left undisturbed (nonhandled, N-H). Corticosterone levels of mothers and pups were measured at the end of the last manipulation session. Corticosterone levels were higher in SM mothers, differing from both those of CB and of control dams; CB pups showed the highest corticosterone levels in comparison with the pups belonging to the other groups. Maternal behavior observed as furthest as possible from the daily separation session did not differ among the three groups. The behavioral response to 0.5 mg/kg of apomorphine in 15-day-old pups was enhanced in both CB and SM animals, which suggests an alteration of dopaminergic functioning. Finally, adult CB and SM male mice showed an increase in the percentage of time and entries into the open arms of the plus-maze in comparison to nonhandled males. This study indicates that exposure to ecologically relevant stimuli elicited a stress response in lactating dams. This "social stress" brings about short- and long-term effects in the offspring, even in the absence of any direct manipulation of the pups. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 44: 230,237, 2004. [source] DNA adduct kinetics in reproductive tissues of DNA repair proficient and deficient male mice after oral exposure to benzo(a)pyreneENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2010Nicole Verhofstad Abstract Benzo(a)pyrene (B[a]P) can induce somatic mutations, whereas its potential to induce germ cell mutations is unclear. There is circumstantial evidence that paternal exposure to B[a]P can result in germ cell mutations. Since DNA adducts are thought to be a prerequisite for B[a]P induced mutations, we studied DNA adduct kinetics by 32P-postlabeling in sperm, testes and lung tissues of male mice after a single exposure to B[a]P (13 mg/kg bw, by gavage). To investigate DNA adduct formation at different stages of spermatogenesis, mice were sacrificed at Day 1, 4, 7, 10, 14, 21, 32, and 42 after exposure. In addition, DNA repair deficient (Xpc,/,) mice were used to study the contribution of nucleotide excision repair in DNA damage removal. DNA adducts were detectable with highest levels in lung followed by sperm and testis. Maximum adduct levels in the lung and testis were observed at Day 1 after exposure, while adduct levels in sperm reached maximum levels at ,1 week after exposure. Lung tissue and testis of Xpc,/, mice contained significantly higher DNA adduct levels compared to wild type (Wt) mice over the entire 42 day observation period (P < 0.05). Differences in adduct half-life between Xpc,/, and Wt mice were only observed in testis. In sperm, DNA adduct levels were significantly higher in Xpc,/, mice than in Wt mice only at Day 42 after exposure (P = 0.01). These results indicate that spermatogonia and testes are susceptible for the induction of DNA damage and rely on nucleotide excision repair for maintaining their genetic integrity. Environ. Mol. Mutagen. 2010. © 2009 Wiley-Liss, Inc. [source] Oral toxicity of the cyanobacterial toxin cylindrospermopsin in mice: Long-term exposure to low dosesENVIRONMENTAL TOXICOLOGY, Issue 6 2006A. Sukenik Abstract The hepatotoxin cylindrospermopsin, a sulfated-guanidinium alkaloid with substituted dioxypyrimidine (uracil) moiety, was isolated from several cyanobacteria species. The acute toxicity of cylindrospermopsin was well established based on intraperitoneal and oral exposure; however, only a few long-term subacute exposure studies were performed to permit a reliable guideline value for cylindrospermopsin in drinking water. In the study reported herein, female and male mice were exposed to cylindrospermopsin in their drinking water. Cylindrospermopsin-containing, Aphanizomenon ovalisporum (cyanobacterium)-free medium was provided as the only source of drinking water, whereas a control group was given a fresh medium for cyanobacteria as drinking water. Over a period of 42 weeks, experiment groups were exposed to cylindrospermopsin concentration, gradually increased from 100 to 550 ,g L,1 (daily exposure ranged between 10 and 55 ,g kg,1 day,1). Body and organ weights were recorded, and serum and hematology analyses were performed 20 and 42 weeks after the beginning of the experiment. The most pronounced effect of cylindrospermopsin was elevated hematocrit levels in both male and female mice after 16 weeks of exposure to cylindrospermopsin. The observed changes in the hematocrit level were accompanied by deformation of red blood cells, which were changed into acanthocyte. Based on these results, a daily cylindrospermopsin dose of 20 ,g kg,1 day,1 (equivalent to 200 ,g L,1) is proposed as the lowest-observed-adverse-effect level for both male and female mice. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 575,582, 2006. [source] Oral toxicity of the cyanobacterial toxin cylindrospermopsin in male Swiss albino mice: Determination of no observed adverse effect level for deriving a drinking water guideline valueENVIRONMENTAL TOXICOLOGY, Issue 2 2003A. R. Humpage Abstract The cyanobacterial toxin cylindrospermopsin (CYN) is a frequent contaminant of freshwaters throughout the world, including those that are sources of drinking water. The first cases of human poisoning attributed to this toxin occurred from a treated drinking water supply in Queensland, Australia, in 1979. The toxin causes extensive damage to the liver, kidneys, spleen, heart, and other organs. It is known to be a potent protein synthesis inhibitor, but there is mounting evidence for genotoxicity and that it metabolizes to even more toxic forms. As part of a risk assessment process leading to a guideline for a safe drinking water level for this toxin, we performed a series of experiments to determine a no-observed-adverse-effect level (NOAEL) for this toxin. In the first trial male mice were exposed to CYN-containing cyanobacterial extract in their drinking water (0,657 ,g CYN kg,1 day,1) for 10 weeks. In the second trial mice received purified CYN by daily gavage (0,240 ,g CYN kg,1 day,1) for 11 weeks. Body and organ weights were recorded; urine, serum, and hematology analyses were performed; and histopathological examination of tissues was carried out. Body weights were significantly increased at low doses (30 and 60 ,g kg,1 day,1) and decreased at high doses (432 and 657 ,g kg,1 day,1). Liver and kidney weights were significantly increased at doses of 240 ,g kg,1 day,1 and 60 ,g kg,1 day,1, respectively. Serum bilirubin levels were significantly increased and bile acids significantly decreased at doses of 216 ,g kg day,1 and greater. Urine total protein was significantly decreased at doses above 60 ,g kg,1 day,1. The kidney appeared to be the more sensitive organ to this toxin. If it is assumed that increased organ weights and changes in functional capacity are responses to an underlying toxic effect, then the NOAEL based on this data is 30 ,g kg,1 day,1, which, with standard calculations and uncertainty factors, provides a proposed guideline safety value of 1 ,g/L in drinking water. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 94,103, 2003. [source] Genotoxicity in wood mice (Apodemus sylvaticus) along a pollution gradient: Exposure-, age-, and gender-related effectsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2006Jan Scheirs Abstract We investigated the effects of environmental pollution on genetic damage in wood mice (Apodemus sylvaticus) by means of the comet assay, with special attention to the role of age and gender as potential confounding variables. The present study was carried out at four sites along a pollution gradient in the vicinity of Antwerp (Belgium), with a nonferrous smelter as the main pollution source. We measured the concentration of heavy metals (Cd, Co, Cr, Cu, Fe, Mn, Pb, and Zn) in mouse liver and kidney and the concentration of organochlorine compounds (polychlorinated biphenyls and 1,1-dichloro-2,2-bis(p -chlorophenyl)ethylene) in mouse muscle tissue to assess individual exposure. Cadmium exposure was very high at the sites closest to the smelter, and exposure to this metal decreased with increasing distance from the smelter. Exposure to the other pollutants was low to moderate at the different sites. Genetic damage was higher in mice from populations in the vicinity of the nonferrous smelter compared with that in the control populations. A significant increase in genetic damage with age was observed at the most polluted sites, but not at the control sites. Genetic damage was higher in male mice than in female mice at the most polluted site, but not at the other areas. Yet, no obvious relationship was found between individual pollutant levels and individual genetic damage levels. We conclude that the comet assay can be used to compare genotoxicity at the population level if the confounding variables of gender and age are taken into account. However, its use for individual health risk assessment remains questionable. [source] A direct main olfactory bulb projection to the ,vomeronasal' amygdala in female mice selectively responds to volatile pheromones from malesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2009Ningdong Kang Abstract The main olfactory system, like the accessory olfactory system, responds to pheromones involved in social communication. Whereas pheromones detected by the accessory system are transmitted to the hypothalamus via the medial (,vomeronasal') amygdala, the pathway by which pheromones are detected and transmitted by the main system is not well understood. We examined in female mice whether a direct projection from mitral/tufted (M/T) cells in the main olfactory bulb (MOB) to the medial amygdala exists, and whether medial amygdala-projecting M/T cells are activated by volatile urinary odors from conspecifics or a predator (cat). Simultaneous anterograde tracing using Phaseolus vulgaris leucoagglutinin and Fluoro-Ruby placed in the MOB and accessory olfactory bulb (AOB), respectively, revealed that axons of MOB M/T cells projected to superficial laminae of layer Ia in anterior and posterodorsal subdivisions of the medial amygdala, whereas projection neurons from the AOB sent axons to non-overlapping, deeper layer Ia laminae of the same subdivisions. Placement of the retrograde tracer cholera toxin B into the medial amygdala labeled M/T cells that were concentrated in the ventral MOB. Urinary volatiles from male mice, but not from female conspecifics or cat, induced Fos in medial amygdala-projecting MOB M/T cells of female subjects, suggesting that information about male odors is transmitted directly from the MOB to the ,vomeronasal' amygdala. The presence of a direct MOB-to-medial amygdala pathway in mice and other mammals could enable volatile, opposite-sex pheromones to gain privileged access to diencephalic structures that control mate recognition and reproduction. [source] Individual vulnerability to escalated aggressive behavior by a low dose of alcohol: decreased serotonin receptor mRNA in the prefrontal cortex of male miceGENES, BRAIN AND BEHAVIOR, Issue 1 2010S. Chiavegatto Low to moderate doses of alcohol consumption induce heightened aggressive behavior in some, but not all individuals. Individual vulnerability for this nonadaptive behavior may be determined by an interaction of genetic and environmental factors with the sensitivity of alcohol's effects on brain and behavior. We used a previously established protocol for alcohol oral self-administration and characterized alcohol-heightened aggressive (AHA) mice as compared with alcohol non-heightened (ANA) counterparts. A week later, we quantified mRNA steady state levels of several candidate genes in the serotonin [5-hydroxytryptamine (5-HT)] system in different brain areas. We report a regionally selective and significant reduction of all 5-HT receptor subtype transcripts, except for 5-HT3, in the prefrontal cortex of AHA mice. Comparable gene expression profile was previously observed in aggressive mice induced by social isolation or by an anabolic androgenic steroid. Additional change in the 5-HT1B receptor transcripts was seen in the amygdala and hypothalamus of AHA mice. In both these areas, 5-HT1B mRNA was elevated when compared with ANA mice. In the hypothalamus, AHA mice also showed increased transcripts for 5-HT2A receptor. In the midbrain, 5-HT synthetic enzyme, 5-HT transporter and 5-HT receptors mRNA levels were similar between groups. Our results emphasize a role for postsynaptic over presynaptic 5-HT receptors in mice which showed escalated aggression after the consumption of a moderate dose of alcohol. This gene expression profile of 5-HT neurotransmission components in the brain of mice may suggest a vulnerability trait for alcohol-heightened aggression. [source] Hematopoietic mobilization in mice increases the presence of bone marrow,derived hepatocytes via in vivo cell fusion,HEPATOLOGY, Issue 1 2006Oscar Quintana-Bustamante The mechanisms for in vivo production of bone marrow,derived hepatocytes (BMDHs) remain largely unclear. We investigated whether granulocyte colony,stimulating factor (G-CSF),mediated mobilization of hematopoietic cells increases the phenomenon. Recurrent liver injury in mice expressing green fluorescent protein (EGFP) in all hematopoietic-derived cells was produced by 3 months of carbon tetrachloride (CCL4) injections. Histologically, there were necrotic foci with histiocyte-rich infiltrates, but little oval cell proliferation. Subsequently, some animals were mobilized with G-CSF for 1, 2, or 3 weeks. Animals were sacrificed 1 month after growth factor treatment. BMDH percentages were lower than previously reported, though G-CSF mobilization significantly augmented BMDH production in injured livers. BMDHs originating from in vivo fusion were evaluated by transplanting female EGFP+ cells into male mice. Binucleated, EGFP+ hepatocytes with one Y chromosome, indicating fusion, were identified. In conclusion, (1) mobilization of hematopoietic cells increases BMDH production and (2) as with the FAH-null model, the first model demonstrating hematopoietic/hepatocyte fusion, recurring CCl4 -induced injury has macrophage-rich infiltrates, a blunted oval cell response, and a predominantly in vivo fusion process for circulating cell engraftment into the liver. These findings open the possibility of using hematopoietic growth factors to treat nonhematopoietic degenerative diseases. (HEPATOLOGY 2006;43:108,116.) [source] Voluntary exercise induces anxiety-like behavior in adult C57BL/6J mice correlating with hippocampal neurogenesisHIPPOCAMPUS, Issue 3 2010Johannes Fuss Abstract Several studies investigated the effect of physical exercise on emotional behaviors in rodents; resulting findings however remain controversial. Despite the accepted notion that voluntary exercise alters behavior in the same manners as antidepressant drugs, several studies reported opposite or no effects at all. In an attempt to evaluate the effect of physical exercise on emotional behaviors and brain plasticity, we individually housed C57BL/6J male mice in cages equipped with a running wheel. Three weeks after continuous voluntary running we assessed their anxiety- and depression-like behaviors. Tests included openfield, dark-light-box, elevated O-maze, learned helplessness, and forced swim test. We measured corticosterone metabolite levels in feces collected over a 24-h period and brain-derived neurotrophic factor (BDNF) in several brain regions. Furthermore, cell proliferation and adult hippocampal neurogenesis were assessed using Ki67 and Doublecortin. Voluntary wheel running induced increased anxiety in the openfield, elevated O-maze, and dark-light-box and higher levels of excreted corticosterone metabolites. We did not observe any antidepressant effect of running despite a significant increase of hippocampal neurogenesis and BDNF. These data are thus far the first to indicate that the effect of physical exercise in mice may be ambiguous. On one hand, the running-induced increase of neurogenesis and BDNF seems to be irrelevant in tests for depression-like behavior, at least in the present model where running activity exceeded previous reports. On the other hand, exercising mice display a more anxious phenotype and are exposed to higher levels of stress hormones such as corticosterone. Intriguingly, numbers of differentiating neurons correlate significantly with anxiety parameters in the openfield and dark-light-box. We therefore conclude that adult hippocampal neurogenesis is a crucial player in the genesis of anxiety. © 2009 Wiley-Liss, Inc. [source] Sex-dependent effects of 56Fe irradiation on contextual fear conditioning in C57BL/6J miceHIPPOCAMPUS, Issue 1 2010Laura Villasana Abstract Effects of irradiation on hippocampal function have been mostly studied in male rodents and relatively little is known about potential effects of irradiation on hippocampal function in female rodents. Moreover, although the long-term effects of clinical radiation on cognitive function have been well established, the effects of other forms of irradiation, such as high charged, high energy radiation (HZE particles) that astronauts encounter during space missions have not been well characterized. In this study we compared the effects of 56Fe irradiation on fear conditioning in C57BL/6J female and male mice. Hippocampus-dependent contextual fear conditioning was impaired in female mice but improved in male mice following 56Fe irradiation. Such impairment was not seen for hippocampus-independent cued fear conditioning. Thus, the effects of 56Fe irradiation on hippocampus-dependent contextual fear conditioning are critically modulated by sex. © 2009 Wiley-Liss, Inc. [source] The hinge region fragment of immunoglobulin G improves immunogenicity of recombinant gonadotrophin-releasing hormone conjugated to the T-helper epitope in designing peptide vaccinesIMMUNOLOGY, Issue 1pt2 2009Jinshu Xu Summary In our previous study, the hinge fragment (225,232/225,,232,) of human immunoglobulin G1 (IgG1) was used as a space peptide linker for synthesizing the GnRH3,hinge,MVP chimeric peptide, whereby three repeated gonadotrophin-releasing hormone (GnRH) units and a T-cell epitope from measles virus fusion protein (MVP) were amide-bond-linked at the N and C terminus, respectively, to the hinge peptide for producing anti-GnRH antibody responses. To investigate whether or not the hinge region fragment can improve the immunogenicity of GnRH, we further synthesized and purified GnRH3,hinge,MVP, GnRH3,hinge and GnRH3,MVP using recombinant DNA technology. Under high pH conditions, GnRH3,hinge,MVP was capable of forming double-chain structures. Immunization of male mice with the immunogens of GnRH3,hinge,MVP resulted in the generation of high-titre antibodies specific for GnRH. The synthetic GnRH3,hinge and GnRH3,MVP induced a lower titre of anti-GnRH antibody than GnRH3,hinge,MVP. This was followed by a decrease in serum testosterone levels, which resulted in a low level of expression of the relaxin-like factor gene in the testis. Our data suggest that peptide and T-cell epitopes oriented at the N-terminus or C-terminus of hinge peptides simplify the antigenic peptide conjugates and may be considered as potential synthetic immunogens. [source] Airway hyper-reactivity mediated by B-1 cell immunoglobulin M antibody generating complement C5a at 1 day post-immunization in a murine hapten model of non-atopic asthmaIMMUNOLOGY, Issue 2 2004Ivana Kawikova Summary Contact skin immunization of mice with reactive hapten antigen and subsequent airway challenge with the same hapten induces immediate airflow obstruction and subsequent airway hyper-reactivity (AHR) to methacholine challenge, which is dependent on B cells but not on T cells. This responsiveness to airway challenge with antigen is elicited as early as 1 day postimmunization and can be adoptively transferred to naïve recipients via 1-day immune cells. Responses are absent in 1-day immune B-cell-deficient JH,/, mice and B-1 B-cell-deficient xid male mice, as well as in recipients of 1-day immune cells depleted of cells with the B-1 cell phenotype (CD19+ B220+ CD5+). As B-1 cells produce immunoglobulin M (IgM), we sought and found significantly increased numbers of anti-hapten IgM-producing cells in the spleen and lymph nodes of 1-day immune wild-type mice, but not in xid mice. Then, we passively immunized naive mice with anti-hapten IgM monoclonal antibody and, following airway hapten challenge of the recipients, we showed both immediate airflow obstruction and AHR. In addition, AHR was absent in complement C5 and C5a receptor-deficient mice. In summary, this study of the very early elicited phase of a hapten asthma model suggests, for the first time, a role of B-1 cells in producing IgM to activate complement to rapidly mediate asthma airway reactivity only 1 day after immunization. [source] The effect of paternal heat stress on protein profiles of pre-implantation embryos in the mouseINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 3 2005B. ZHU Summary The study was undertaken to compare the protein profiles of [35S]-methionine-labelled control-sired embryos with heat-sired embryos at 7, 14 or 21 days after mature fertile B6CBF F1 male mice were kept at 36 ± 0.3 °C and 62 ± 2.7% relative humidity for 24 h. One-dimensional gel electrophoresis and autoradiographs were used to examine the protein profiles between the two-cell embryos and the blastocysts. The results obtained demonstrate that paternal heat stress 7 or 14 days earlier did not apparently affect protein patterns of two-cell embryos, four-cell to eight-cell embryos, morulae or blastocysts. However, 21 days earlier, there were changes in protein patterns of two-cell embryos and abnormal embryos, but not the morulae. To further support and extend these results, two-dimensional gel electrophoresis and phosphorimaging were employed and the results obtained show that paternal heat stress 21 days before mating affected protein profiles of two-cell embryos and morulae in the mouse. Together, these findings have indicated that paternal heat stress affects most but not all protein patterns of pre-implantation embryos, which strongly supports our previous results demonstrating that paternal heat stress significantly reduced the developmental proportion of pre-implantation embryos in the mouse. [source] | ||||||||||||||||||||||||||||||||||||||||