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Modified Mice (modified + mouse)
Kinds of Modified Mice Selected AbstractsInfarct Size Assessment in MiceECHOCARDIOGRAPHY, Issue 1 2007Marielle 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] Heart specific up-regulation of genes for B-type and C-type natriuretic peptide receptors in diabetic miceEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2006C. Christoffersen Abstract Background, Diabetes may cause cardiomyopathy characterized by cardiac fibrosis. Recent studies of genetically modified mice have elucidated a role of the natriuretic peptides (NP), type-A and type-B (ANP and BNP), and their common receptor [natriuretic peptide receptor (NPR), type-A] in development of cardiac fibrosis. The role of NP type-C (CNP) and NPR type-B (NPR-B) in the heart is less well established. In this study we examined if diabetes alters heart expression of the genes encoding the NP and its receptors. Materials and methods, Cardiac mRNA was quantified by real-time PCR in diabetic streptozotocin (STZ)-treated and ob/ob- mice and nondiabetic control mice. Results, The ob/ob -mice with type-II diabetes displayed highly significant increases of the cardiac mRNA expression of NPR-B and NPR-C while the expression levels of NPR-A, ANP, BNP, and CNP mRNA were similar in ob/ob -mice and controls. Mice with STZ-induced type-I diabetes also showed an increase of heart NPR-B mRNA expression at 12 weeks, but not at 3, 6 or 9 weeks after STZ-treatment. The ANP and NPR-C mRNA expressions were only altered after 3 weeks, whereas BNP, CNP and NPR-A mRNA expressions were not altered in STZ-treated-mouse hearts at any of the time points. Conclusions, The results show that diabetes in mice confers increased NPR-B gene expression in the heart, suggesting that increased NPR-B signalling may affect development of diabetic cardiomyopathy. [source] Enhanced B-cell activation mediated by TLR4 and BCR crosstalk,EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2008Susana Minguet Abstract Despite the important role of B lymphocytes as a bridge between the innate and the adaptive immune system, little is known regarding lipopolysaccharide (LPS) recognition, activation of signalling networks or conceivable cooperation between LPS and the B-cell antigen receptor (BCR). Here, we show that primary B cells can efficiently discriminate between different LPS chemotypes, responding with at least 100-fold higher sensitivity to rough-form LPS compared with smooth-form LPS. Using genetically modified mice, we demonstrate that B lymphocytes recognize all LPS chemotypes via Toll-like receptor 4 (TLR4). In addition, we dissect the signalling pathways that lead to CD69 upregulation upon TLR4 and BCR activation in primary B cells. Our data suggest that TLR4 and BCR induce CD69 transcription via two distinct sets of signalling molecules, exerting quantitative and qualitative differences in B-cell activation. Finally, we show that simultaneous stimulation of TLR4 and BCR additively elevates B-cell activation. In contrast, co-engagement of TLR4 and BCR by antigen-coupled LPS synergistically enhances activation of B cells, pointing out attractive targets for signalling crosstalk in B lymphocytes. [source] Transgenic and knock-out mouse pups: the growing need for behavioral analysisGENES, BRAIN AND BEHAVIOR, Issue 3 2002I. Branchi Few laboratories working with transgenic and knock-out mice analyze the neurobehavioral consequences of genetic manipulation in early ontogeny. However, the study of behavioral endpoints during the early postnatal period in genetically modified mice is important not only to assess possible developmental abnormalities, but also to better understand and disentangle the effects of genetic manipulations in adulthood. We propose that the assessment of neurobehavioral development represents an appropriate strategy to identify possible compensatory and/or unexpected effects. Nowadays, a large number of experimental protocols that take into account the practical constraints imposed by the peculiar physiological and behavioral responses of an immature subject are available to assess the neurobehavioral profile of developing mice. While this knowledge should be applied to the field of transgenic and knock-out mice in general, it should be recommended, in particular, for the study of mouse models of neurodevelopmental disorders. [source] Model of frequent, recurrent, and spontaneous seizures in the intact mouse hippocampusHIPPOCAMPUS, Issue 8 2004M. Derchansky Abstract This study presents a model of chronic, recurrent, spontaneous seizures in the intact isolated hippocampal preparation from mice aged P8,P25. Field activity from the CA1 pyramidal cell layer was recorded and recurrent, spontaneous seizure-like events (SLEs) were observed in the presence of low Mg2+ (0.25 mM) artificial cerebrospinal fluid (ACSF). Hippocampi also showed interictal epileptiform discharges (IEDs) of 0.9,4.2 Hz occurring between seizures. No age-specific differences were found in SLE occurrence (2 SLEs per 10 min, on average), duration, and corresponding frequencies. After long exposure to low Mg2+ ACSF (>3 h), SLEs were completely reversible within minutes with the application of normal (2 mM Mg2+) ACSF. The AMPA antagonist, CNQX, blocked all epileptiform activity, whereas the NMDA antagonist, APV, did not. The ,-aminobutyric acid (GABA)A antagonist, bicuculline, attenuated and fragmented SLEs, implicating interneurons in SLE generation. The L-type Ca2+ blocker, nifedipine, enhanced epileptiform activity. Analysis of dual site recordings along the septotemporal hippocampus demonstrated that epileptiform activity began first in the temporal pole of the hippocampus, as illustrated by disconnection experiments. Once an SLE had been established, however, the septal hippocampus was sometimes seen to lead the epileptiform activity. The whole hippocampus with intact local circuitry, treated with low Mg2+, provides a realistic model of recurrent spontaneous seizures, which may be used, in normal and genetically modified mice, to study the dynamics of seizures and seizure evolution, as well as the mechanisms of action of anti-epileptic drugs and other therapeutic modalities. © 2004 Wiley-Liss, Inc. [source] Role of shelterin in cancer and agingAGING CELL, Issue 5 2010Paula Martínez Summary Mammalian telomeres are formed by tandem repeats of the TTAGGG sequence bound by a specialized six-protein complex known as shelterin, which has fundamental roles in the regulation of telomere length and telomere capping. In the past, the study of mice genetically modified for telomerase components has been instrumental to demonstrate the role of telomere length in cancer and aging. Recent studies using genetically modified mice for shelterin proteins have highlighted an equally important role of telomere-bound proteins in cancer and aging, even in the presence of proficient telomerase activity and normal telomere length. In this review, we will focus on recent findings, suggesting a role of shelterin components in cancer and aging. [source] Lifespan extension in genetically modified miceAGING CELL, Issue 4 2009Warren Ladiges Summary Major advances in aging research have been made by studying the effect of genetic modifications on the lifespan of organisms, such as yeast, invertebrates (worms and flies) and mice. Data from yeast and invertebrates have been the most plentiful because of the ease in which genetic manipulations can be made and the rapidity by which lifespan experiments can be performed. With the ultimate focus on advancing human health, testing genetic interventions in mammals is crucial, and the mouse has proven to be the mammal most amenable to this task. Lifespan studies in mice are resource intensive, requiring up to 4 years to complete. Therefore, it is critical that a set of scientifically-based criteria be followed to assure reliable results and establish statistically significant findings so other laboratories can replicate and build on the data. Only then will it be possible to confidently determine that the genetic modification extends lifespan and alters aging. [source] Functional ,glial' GLYT1 glycine transporters expressed in neuronsJOURNAL OF NEUROCHEMISTRY, Issue 3 2010Luca Raiteri J. Neurochem. (2010) 114, 647,653. Abstract Glycine transporter 1 (GLYT1) and GLYT2 are the glycine transporters in CNS. While GLYT2 is largely expressed in glycinergic neurons, GLYT1 has long been considered to be exclusively present in glial cells. There is increasing evidence that significant amounts of the ,glial' transporter also exist on neurons, particularly on pre-synaptic nerve endings of glutamatergic neurons. The functions of ,neuronal GLYT1' may be manifold and are discussed in this review. Of major interest are the interactions between neuronal GLYT1 and glutamatergic receptors of the NMDA type the activity of which is modulated not only by astrocytic GLYT1 but also by neuronal GLYT1. Pathophysiological roles and therapeutic implications of neuronal GLYT1 are emerging from recent studies with genetically modified mice, particularly with animals lacking forebrain neuron-specific GLYT1 transporters. These mutant mice exhibit promnesic phenotypes reflecting enhancement of NMDA receptor function, as it occurs following administration of GLYT1 inhibitors. Inactivation of neuronal GLYT1 in the forebrain may represent an effective therapeutic intervention for the treatment of schizophrenia. [source] Intracellular survival pathways in the liverLIVER INTERNATIONAL, Issue 10 2006Tom Luedde Abstract: Recent studies have drawn attention to cytokines as important modulators of hepatocyte cell death during acute and chronic liver disease. Through interaction with cell surface receptors, they activate specific intracellular pathways that influence cell fate in different manners. For example, tumor necrosis factor not only induces proapoptotic signals via the caspase cascade but also activates intracellular survival pathways, namely the nuclear factor (NF)-,B pathway. In this article, we will focus on the function of the NF-,B pathway in liver physiology and pathology. Especially, recent data based on experiments with genetically modified mice will be discussed, which demonstrated important and controversial functions of this pathway e.g. in cytokine-mediated hepatocyte apoptosis, ischemia-reperfusion injury, liver regeneration and the development of hepatocellular carcinoma. Moreover, the role of the interleukin-6 pathway and its possible protective function in the context of liver failure will be summarized. [source] Monocyte Chemoattractant Protein-1 (CCL2) in Inflammatory Disease and Adaptive Immunity: Therapeutic Opportunities and ControversiesMICROCIRCULATION, Issue 3-4 2003CHRISTINE DALY ABSTRACT Monocyte chemoattractant protein (MCP)-1 (CCL2) specifically attracts monocytes and memory T cells. Its expression occurs in a variety of diseases characterized by mononuclear cell infiltration, and there is substantial biological and genetic evidence for its essential role in atherosclerosis and multiple sclerosis. Despite intensive screening, there are as yet no small-molecule antagonists of the receptor of MCP-1/CCL2, CCR2. However, biological agents, including antibodies and inhibitory peptides, have been developed and may be useful for these indications. Recent evidence from genetically modified mice indicates that MCP-1 and CCR2 have unanticipated effects on T helper (Th) cell development. However, unlike the identical phenotypes of MCP-1/CCL2,/, and CCR2,/, mice in inflammatory diseases, the phenotypes of these mice are disparate in adaptive immunity: MCP-1 stimulates Th2 polarization, whereas CCR2 activation stimulates Th1 polarization. This presents both a challenge and an opportunity for targeting the MCP-1/CCL2/CCR2 axis in disease. [source] 4141: Visual phenotyping at the "Institut Clinique de la Souris"ACTA OPHTHALMOLOGICA, Issue 2010MJ ROUX Purpose Visual diseases come in many flavors, with a large variety of affected tissues (eye anterior segment, retina, optic nerve, cortex ,), ages of onset, rate of progression and causal factors. In Western countries, if the majority of these diseases are now curable, millions of people are still affected by blindness or low vision, as many retinal diseases (age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, glaucoma,) still lack efficient treatments. In a facility devoted to mouse phenotyping as the Mouse Clinic Institute (MCI), it is thus of major importance to propose an efficient visual phenotyping platform, to pick up visual defects in screened mutants, to assess the beneficial effects of potential treatments or the eventual adverse effects of drugs targeting the CNS. Methods Methods: Mouse mutant lines from the Eumodic European project, as well as lines from specific academic projects, go through clinical observation (slit lamp, fundus imaging) in the context of a behavioral phenotyping pipeline, or are assessed in more details with angiography, optomotor response, electroretinography, retinal histology and/or immunohistochemistry. Results To illustrate the possibilities offered by the MCI visual phenotyping platform, we will present results obtained from various projects, as well as the validation of electroretinography protocols to follow dark adaptation and the effect of acute drug injections. Conclusion In an environment allowing for an in depth phenotyping, from behavior to biochemistry, metabolism and cardiology, the MCI visual phenotyping platform provides a comprehensive set of tests to get the most out of genetically modified mice. [source] 2126: Retinal and cortical functions in adult mice lacking cannabinoid receptorsACTA OPHTHALMOLOGICA, Issue 2010C CASANOVA Purpose Cannabinoid receptor type 1 (CB1R) has been localized in the adult retina of rodents. It is expressed in cones, horizontal, bipolar, some amacrine and ganglion cells. The expression of the cannabinoid receptor type 2 (CB2R) mRNA in the retina of adult rats was also reported. The goal of the present study was to investigate the functional roles of CB1R and CB2R in the retina by comparing retinal electrophysiological responses and cortical optical signals in normal and genetically modified mice. Methods Experiments were conducted on four different groups of C57BL/6 mice: CB1R wild type (WT), CB1R knockout (KO), CB2R WT and KO. Scotopic electroretinograms (ERG) luminance-response functions and photopic ERGs were recorded. In a subset of CB1 groups, intrinsic signals acquired by optical brain imaging were used to determine spatial frequency, contrast sensitivity and retinotopic maps in the visual cortex. Results The CB1R KO retina showed a stronger photopic response. No differences were observed for scotopic responses. For the CB2R groups, the scotopic b-wave response was stronger in the KO mice. No differences could be seen between visual cortices maps with respect to SF and contrast sensitivity. Retinotopic maps differed only along the azimuth. Significant differences were observed between hemodynamic response functions. Conclusion These results indicate that CB receptors can play a regulatory effect on the neurovascular coupling at the retinal and cortical levels and on the functional organization of the mice visual cortex along the azimuth Axis.(NSERC) [source] Mouse isolated perfused heart: Characteristics and cautionsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2003Fiona J Sutherland Summary 1.,Owing to the considerable potential for manipulating the murine genome and, as a consequence, the increasing availability of genetically modified models of cardiovascular diseases, the mouse is fast becoming a cornerstone of animal research. However, progress in the use of various murine preparations is hampered by the lack of facilities and skills for the adequate physiological assessment of genetically modified mice. 2.,We have attempted to address this problem by refining and characterizing a mouse isolated heart preparation that was originally developed for use with larger hearts. 3.,We used the isolated buffer-perfused Langendorff preparation (perfused at constant flow or constant pressure) to characterize: (i) the frequency,response characteristics; (ii) heart isolation conditions; (iii) perfusion chamber conditions; (iv) temperature,function relationships; (v) stability over extended periods of perfusion; (vi) perfusate calcium,function relationships; (vii) pressure,volume relationships; (viii) pressure,rate relationships; and (ix) flow,function relationships. [source] Cardiovascular and renal phenotyping of genetically modified mice: A challenge for traditional physiologyCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2003Sharyn M Fitzgerald Summary 1.,The advent of techniques to genetically modify experimental animals and produce directed mutations in both a conditional and tissue-specific manner has dramatically opened up new fields for physiologists in cardiovascular and renal research. 2.,A consequence of altering the genetic background of mice is the difficulty in predicting the phenotypic outcome of the genetic mutation. We therefore suggest that physiologists may need to change their current experimental paradigms to face this new era. Hence, our aim is to propose a complementary research philosophy for physiologists working in the post-genomic era. That is, instead of using strictly hypothesis-driven research philosophies, one will have to perform screening studies of mutant mice, within a field of interest, to find valuable phenotypes. Once a relevant phenotype is found, in-depth studies of the underlying mechanisms should be performed. These follow-up studies should be performed using a traditional hypothesis-driven research philosophy. 3.,The rapidly increasing availability of mutated mouse models of human disease also necessitates the development of techniques to characterize these various mouse phenotypes. In particular, the miniaturization and refinement of techniques currently used to study the renal and cardiovascular system in larger animals will be discussed in the present review. Hence, we aim to outline what techniques are currently available and should be present in a laboratory to screen and study renal and cardiovascular phenotypes in genetically modified mice, with particular emphasis on methodologies used in the intact, conscious animal. [source] Transglutaminase 1-deficient recessive lamellar ichthyosis associated with a LINE-1 insertion in Jack Russell terrier dogsBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2009K.M. Credille Summary Background, Congenital, nonepidermolytic cornification disorders phenotypically resembling human autosomal recessive ichthyosis have been described in purebred dog breeds, including Jack Russell terrier (JRT) dogs. One cause of gene mutation important to humans and dogs is transposon insertions. Objectives, To describe an autosomal recessive, severe nonepidermolytic ichthyosis resembling lamellar ichthyosis (LI) in JRT dogs due to insertion of a long interspersed nucleotide element (LINE-1) in the transglutaminase 1 (TGM1) gene. Methods, Dogs were evaluated clinically, and skin samples were examined by light and electron microscopy. Phenotypic information and genotyping with a canine microsatellite marker suggested TGM1 to be a candidate gene. Genomic DNA samples and cDNA generated from epidermal RNA were examined. Consequences of the mutation were evaluated by Western blotting, quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme activity from cultured keratinocytes. Results, Affected dogs had generalized severe hyperkeratosis. Histological examination defined laminated to compact hyperkeratosis without epidermolysis; ultrastructurally, cornified envelopes were thin. Affected dogs were homozygous for a 1980-bp insertion within intron 9 of TGM1. The sequence of the insertion was that of a canine LINE-1 element. Quantitative RT-PCR indicated a significant decrease in TGM1 mRNA in affected dogs compared with wild-type. TGM1 protein was markedly decreased on immunoblotting, and membrane-associated enzyme activity was diminished in affected dogs. Conclusions, Based on morphological and molecular features, this disease is homologous with TGM1-deficient LI in humans, clinically models LI better than the genetically modified mouse and represents its first spontaneous animal model. This is the first reported form of LI due to transposon insertion. [source] | |||||||||||||