Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Mouse models”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMedDate not supplied

Preliminary evidence of phenytoin-induced alterations in embryonic gene expression in a mouse model.

SWV mouse embryos collected on gestational days (GD) 9:12 and 10:00 following chronic in utero exposure to teratogenic concentrations of phenytoin were utilized for in situ transcription studies of gene expression. The substrate cDNA obtained from the frozen embryo sections was amplified into radiolabelled antisense RNA (RT/aRNA) and used as a probe to screen a panel of 20 cDNA clones representing genes that are important regulators of craniofacial and neural development. The magnitude of alteration in gene expression following phenytoin treatment was determined densitometrically by changes in the hybridization intensity of the aRNA probes to the cDNA clones immobilized to the slot blots. We found that both Wnt-1 and the calcium channel gene were developmentally regulated, as their level of expression decreased significantly between the two collection times. Phenytoin treatment produced a significant downregulation in the level of expression for 25% of the genes examined in the GD 9:12 embryos, including the growth factors TGF-beta and NT3, the proto-oncogene Wnt-1, the nicotinic receptor, and the voltage sensitive calcium channel gene. Additional changes in the coordinate expression of several of the growth and transcription factors were observed at both gestational timepoints. The application of RT/aRNA technology has extended our appreciation of the normal patterns of gene expression during craniofacial and neural development, and provided the first demonstration of multiple coordinate changes in transcription patterns following teratogenic insult.

Analysis of Variance↗
PubMed1992

Profiles of interaction of R(+)/S(-)-zacopride and anxiolytic agents in a mouse model.

The mouse black and white test box was used to measure changes in behaviour in an aversive situation where the administration of R(+)-zacopride (but not S(-)-zacopride) alone decreased aversive responding to the white area. A similar anxiolytic profile of action was observed using parachlorophenylalanine (PCPA), whose effects were antagonised by a co-treatment with R(+)-zacopride and reversed by S(-)-zacopride to an exacerbation of the aversive response. An anxiolytic profile of action was also observed using ondansetron, granisetron, chlordiazepoxide, diazepam, ritanserin, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), E4424 (2-[4-[4-(4-chloro-l-pyrazoyl)butyl]-l-piperazinyl]-pyrimidine), umepsirone, DuP753 (2-n-butyl-4-chloro-5-hydroxy-methyl-1-[2(1H-tetrazol-5-yl) biphenyl-4-yl)methyl)]-imidazole), SQ29,852 ((S)-1-[6-amino-2[hydroxy)(4-phenyl-butyl)phosphinyl]-oxy)-1- nexy]-2-proline), devazepide and guanfacine, and this was retained following co-treatment with PCPA. The anxiolytic profile of action of PCPA was also retained following co-treatment with renzapride which when administered alone failed to modify behaviour. However, the ability of chlordiazepoxide, diazepam, ondansetron and E4424 (but not devazepide, DuP753 or SQ29,852) to reduce aversive responding was inhibited by co-treatment with R(+) and/or S(-)-zacopride. It is concluded that the reduction in aversive responding caused by pharmacological manipulation at the benzodiazepine, 5-HT receptor subtypes 5-HT1A, 5-HT1C/5-HT2 and 5-HT3 (but not at the cholecystokin CCKA or angiotensin receptors or inhibition of angiotensin converting enzyme) can be inhibited by R(+) and S(-)-zacopride. The data is discussed in terms of zacopride having an agonist or partial agonist effect at the 5-HT3 receptor.

Animals↗
PubMedDate not supplied

Genetic mouse models of extended lifespan.

Since 1996, seven genetic mouse models have been reported to show increased lifespan: Ames and Snell dwarf mice, the 'little mouse' (Ghrhr(lit/lit)), mice null for either growth hormone receptor/binding protein (GHR/BP(-/-)) or p66(shc) (p66(shc-/-)), mice heterozygous for the IGF-I receptor (Igf1r(+/-)), and fat-specific insulin receptor knockout mice. In this article, we describe and evaluate these mouse models with respect to their relevance for aging studies. While these seven genetic models all show a significant increase in lifespan, issues of sample size and animal husbandry procedures require further evaluation before firm conclusions can be drawn on the reproducibility of life extension in most of these mouse models. Because data on the age-related pathology and physiological functions are lacking for all of the models, except the dwarf mice, it is too early to conclude that aging is retarded in these mouse models. However, these mouse models are already providing new information about the mechanism underlying mammalian aging.

Aging↗
PubMed2005

Development of a conditional mouse model for head and neck squamous cell carcinoma.

Last decade major advances have been made in the field of mouse model engineering. Newly developed conditional mouse models have overcome important drawbacks in conventional mouse models. Conditional mouse models are especially suited for the development of models of sporadic human carcinomas. These models can control gene (in)activation in a time and/or tissue-specific manner. Here, we review two important conditional mouse model systems, based on the Tet off/on and the Cre-Lox system. Furthermore possible applications of the Cre-Lox system in the development of a mouse model for HNSCC are being discussed. In the future, conditional mouse models for HNSCC can be used in the identification of new key genes in HNSCC tumorigenesis, and would furthermore serve as an indispensable tool for designing new treatment-modalities.

Animals↗
PubMed2006

Genetic mouse models of schizophrenia: from hypothesis-based to susceptibility gene-based models.

Translation of human genetic mutations into genetic mouse models is an important strategy to study the pathogenesis of schizophrenia, identify potential drug targets, and test new drugs for new antipsychotic treatments. Although it is impossible to recapitulate the full spectrum of schizophrenia symptoms in animal models, hypothesis-driven genetic mouse models have been successful in reproducing several schizophrenia-like behaviors and uncovering the roles of specific genes in dopamine and glutamine neurotransmission systems in mediating schizophrenia-like behaviors. Recent discoveries of susceptibility genes for schizophrenia and recognition of cognitive dysfunction as a core feature of schizophrenia and a phenotype of susceptibility for schizophrenia offer opportunities to develop newer genetic mouse models based on susceptibility. This new generation of genetic mouse models could shed light on the etiology of schizophrenia and lead us to new hypotheses, novel diagnostic tools, and more effective therapy.

Animals↗
PubMed1989

Salmonella typhimurium virulence in a burned-mouse model.

Various features of salmonellosis were examined in a burned-mouse model. In this model, which uses an outbred mouse strain, a challenge dose of ca. 100 CFU with any of several strains of Salmonella typhimurium caused a fatal infection. A variety of mutated strains attenuated for virulence in Salmonella-susceptible parenterally infected mice were also attenuated in the burned-mouse model. When administered as live vaccines injected intraperitoneally the same attenuated strains provided between slight and complete protection against subsequent lethal challenge subcutaneously at the site of a burn. The correspondence of results obtained in the burned-mouse model with those seen in other mouse models coupled with the unique advantages of the burned-mouse model argue for the usefulness of the model in studies of salmonellosis and in testing of strains constructed for use as live vaccines.

Animals↗
PubMed2005

Transgenic mouse models for the prevention of breast cancer.

Breast cancer prevention research has made remarkable progress in the past decade. Much of this progress has come from clinical trials. However, in the future to test the many promising agents that are now available, pre-clinical models of breast cancer are needed. Such models are now available. Useful models include rat and mouse models, particularly, the genetically engineered mice (GEM). Many transgenic mouse models have been generated by manipulating growth factors and their receptors, cell cycle regulators, signal transduction pathways, cellular differentiation, oncogenes and tumor suppressor genes. The transgenes are induced to express in the mouse mammary glands under the control of various transgenic promoters, which have respective characteristics in expression pattern and other biological attributes. These models are providing invaluable insight on the molecular mechanisms of breast tumorigenesis. In this review, we discuss the relative relevance of the most commonly used transgenic mouse models for breast cancer prevention studies, and provide examples of how these transgenic models can be used to conduct cancer prevention research. Due to the multi-factor, multi-step nature of breast cancer, many factors should be incorporated into a valid prevention study. However, many barriers to progress must be overcome, including access to and availability of new cancer preventive drugs, and difficulties in conducting studies of combinations of preventive agents.

Animals↗
PubMed1995

Efficacy of AZT therapy in reducing p24 antigen burden in a modified SCID mouse model of HIV infection.

A modified severe combined immunodeficient (SCID) mouse model of HIV infection which utilized multiple reconstitutions with human lymphocytes and a large inoculum of HIV was investigated. This mouse model yielded splenic HIV p24 antigen concentrations detectable by standard clinical means. The concentration of p24 exceeded 600 pg/g of spleen through 4 weeks postinfection. A 1-week course of AZT therapy initiated after infection produced a dose responsive reduction in p24 antigen burden. Up to a 95% reduction in p24 antigen burden was observed following AZT therapy at 50 mg/kg/day, while AZT therapy at 5 and 0.5 mg/kg/day produced 52 and 18% reductions. In vitro and pharmacokinetic evaluations correlated potency and tissue concentrations of AZT with treatment efficacy. Active HIV replication in the SCID mice was suggested by both the recovery of viable virus from SCID spleens, and by the efficacy of a brief course of AZT therapy. This SCID mouse model of HIV infection was more quantitative than previous mouse models that utilize PCR-based techniques for detection of HIV. The high HIV burden in this SCID mouse model allowed reductions in p24 concentration to be monitored in response to AZT therapy. A dose response to AZT therapy was demonstrated, even when the first dose was administered after infection. This result suggests greater sensitivity than in previous models in which pretreatment with AZT was required to produce a protective response. This SCID mouse model may be useful for determining efficacy of experimental HIV therapeutics prior to clinical use. An effective animal model could result in a reduction in cost and more rapid development of effective HIV therapeutics.

Animals↗
PubMed2004

Mouse models of abdominal aortic aneurysms.

Many mouse models of abdominal aortic aneurysms have been developed that use a diverse array of methods for producing the disease, including genetic manipulation and chemical induction. These models could provide insight into potential mechanisms in the development of this disease. Although experimental studies on abdominal aortic aneurysms (AAAs) have used a variety of mammalian and avian approaches, there is an increasing reliance on the use of mice. The models recapitulate some facets of the human disease including medial degeneration, inflammation, thrombus formation, and rupture. Most of the mouse models of AAA are evoked either by genetically defined approaches or by chemical means. The genetic approaches are spontaneous and engineered mutations. These include defects in extracellular matrix maturation, increased degradation of elastin and collagen, aberrant cholesterol homeostasis, and enhanced production of angiotensin peptides. The chemical approaches include the intraluminal infusion of elastase, periaortic incubations of calcium chloride, and subcutaneous infusion of AngII. A common feature of these models is the reduction of AAA incidence and severity by the prophylactic administration of matrix metalloproteinase (MMP) inhibitors or genetically engineered deficiencies of specific members of this proteolytic protein family. The validation of mouse models of AAAs will provide insight into the mechanisms of progression of the human disease.

Angiotensin II↗
PubMed2006

Pathology of genetically engineered mouse models of pancreatic exocrine cancer: consensus report and recommendations.

Several diverse genetically engineered mouse models of pancreatic exocrine neoplasia have been developed. These mouse models have a spectrum of pathologic changes; however, until now, there has been no uniform nomenclature to characterize these changes. An international workshop, sponsored by The National Cancer Institute and the University of Pennsylvania, was held from December 1 to 3, 2004 with the goal of establishing an internationally accepted uniform nomenclature for the pathology of genetically engineered mouse models of pancreatic exocrine neoplasia. The pancreatic pathology in 12 existing mouse models of pancreatic neoplasia was reviewed at this workshop, and a standardized nomenclature with definitions and associated images was developed. It is our intention that this nomenclature will standardize the reporting of genetically engineered mouse models of pancreatic exocrine neoplasia, that it will facilitate comparisons between genetically engineered mouse models and human pancreatic disease, and that it will be broad enough to accommodate newly emerging mouse models of pancreatic neoplasia.

Animals↗
PubMedDate not supplied

Tumor spectrum in the p53 heterozygous zeta globin-promoted Tg.AC (v-Ha-ras) bitransgenic mouse model.

The use of a bitransgenic mouse model for cancer is an effective approach for studying the impact of specific carcinogens and the occurrence of tissue-specific lesions. We studied the novel p53 heterozygous zeta globin-promoted Tg.AC (v-Ha-ras) mouse model because these mice contain a carcinogen-inducible ras oncogene and one functional p53 tumor suppressor allele, both of which occur frequently in human cancers. Our aim was to characterize the short-term control and chemically induced tumor spectrum in this novel model. Mice were placed on basal semipurified diet containing 20% soy protein for 2 weeks prior to random allocation to groups. Subsequently, 15 male and 15 female mice were administered corn oil vehicle alone or containing benzo(a)pyrene (20 mg/kg body weight) via oral gavage 2 times per week for 10 weeks with subsequent observation for 18 weeks. Mice exhibited lesions characteristic of FVB/N, p53 heterozygous and Tg.AC mouse models. However, an array of unique, novel lesions were observed including uterine leiomyosarcomas, mammary gland carcinomas, mammary squamous cell carcinomas, and parotid salivary gland carcinomas suggesting tissue-specific interactions of the 2 genotypes. Thus, this bitransgenic model may provide further insight into the mechanistic interaction of 2 genes commonly mutated in neoplasia.

Alleles↗
PubMed2002

Mouse models for neurological disease.

The mouse has many advantages over human beings for the study of genetics, including the unique property that genetic manipulation can be routinely carried out in the mouse genome. Most importantly, mice and human beings share the same mammalian genes, have many similar biochemical pathways, and have the same diseases. In the minority of cases where these features do not apply, we can still often gain new insights into mouse and human biology. In addition to existing mouse models, several major programmes have been set up to generate new mouse models of disease. Alongside these efforts are new initiatives for the clinical, behavioural, and physiological testing of mice. Molecular genetics has had a major influence on our understanding of the causes of neurological disorders in human beings, and much of this has come from work in mice.

Animals↗
PubMed2004

Application of a non-linear image registration algorithm to quantitative analysis of T2 relaxation time in transgenic mouse models of AD pathology.

Transgenic mouse models have been essential for understanding the pathogenesis of Alzheimer's disease (AD) including those that model the deposition process of beta-amyloid (Abeta). Several laboratories have focused on research related to the non-invasive detection of early changes in brains of transgenic mouse models of Alzheimer's pathology. Most of this work has been performed using regional image analysis of individual mouse brains and pooling the results for statistical assessment. Here we report the implementation of a non-linear image registration algorithm to register anatomical and transverse relaxation time (T2) maps estimated from MR images of transgenic mice. The algorithm successfully registered mouse brain magnetic resonance imaging (MRI) volumes and T2 maps, allowing reliable estimates of T2 values for different regions of interest from the resultant combined images. This approach significantly reduced the data processing and analysis time, and improved the ability to statistically discriminate between groups. Additionally, 3D visualization of intra-regional distributions of T2 of the resultant registered images provided the ability to detect small changes between groups that otherwise would not be possible to detect.

Algorithms↗
PubMed2005

A new mouse model for infantile neuroaxonal dystrophy, inad mouse, maps to mouse chromosome 1.

Infantile neuroaxonal dystrophy (INAD) is a rare autosomal recessive hereditary neurodegenerative disease of humans. So far, no responsible gene has been cloned or mapped to any chromosome. For chromosome mapping and positional cloning of the responsible gene, establishment of an animal model would be useful. Here we describe a new mouse model for INAD, named inad mouse. In this mouse, the phenotype is inherited in an autosomal recessive manner, symptoms occur in the infantile period, and the mouse dies before sexual maturity. Axonal dystrophic change appearing as spheroid bodies in central and peripheral nervous system was observed. These features more closely resembled human INAD than did those of the gad mouse, the traditional mouse model for INAD. Linkage analysis linked the inad gene to mouse Chromosome 1, with the highest LOD score (=128.6) at the D1Mit45 marker, and haplotype study localized the inad gene to a 7.5-Mb region between D1Mit84 and D1Mit25. In this linkage area some 60 genes exist: Mutation of one of these 60 genes is likely responsible for the inad mouse phenotype. Our preliminary mutation analysis in 15 genes examining the nucleotide sequence of exons of these genes did not find any sequence difference between inad mouse and C57BL/6 mouse.

Animals↗
PubMed2003

Tumorigenic potential of carbaryl in the heterozygous p53 knockout mouse model.

The heterozygous p53 knockout mouse model was used to assess whether vascular tumors noted in a 2-year carcinogenicity study in CD-1 mice with carbaryl were induced through a genotoxic mechanism. This knockout mouse model was selected for carbaryl because of the high sensitivity of this model to genotoxic events and its low spontaneous incidence of tumors until 9-12 months of age. Carbaryl was administered continuously via the diet to groups of 20 male heterozygous p53 knockout mice at concentrations of 0, 10, 30, 100, 300, 1000 and 4000 ppm for 180 days. Histopathological examinations revealed no evidence of carbaryl-induced neoplasms of any type. In particular, no neoplastic or preneoplastic changes were noted in the vascular tissue of any of the organs examined. Only neoplasms, recognized as those that occur spontaneously in untreated mice of this strain, were sporadically observed in a few animals from the intermediate dose groups with no evidence of a dose- or treatment-related effect. Therefore, under the conditions of this study, the no-observed-effect level (NOEL) of carbaryl for neoplastic changes in male mice was 4000 ppm (around 716 mg/kg body weight/day). We conclude: (1) carbaryl does not appear to be a genotoxic carcinogen at least in male mice; (2) if the vascular tumors observed in the CD-1 mice are treatment-related, they could have been induced by a non-genotoxic mechanism; (3) the response in transgenic animals may provide useful complementary results to better assess carbaryl's potential genotoxic hazard to humans.

Animals↗
PubMed2006

HIV-1 infection and CD4 T cell depletion in the humanized Rag2-/-gamma c-/- (RAG-hu) mouse model.

BACKGROUND: The currently well-established humanized mouse models, namely the hu-PBL-SCID and SCID-hu systems played an important role in HIV pathogenesis studies. However, despite many notable successes, several limitations still exist. They lack multi-lineage human hematopoiesis and a functional human immune system. These models primarily reflect an acute HIV infection with rapid CD4 T cell loss thus limiting pathogenesis studies to a short-term period. The new humanized Rag2-/-gamma c-/- mouse model (RAG-hu) created by intrahepatic injection of CD34 hematopoietic stem cells sustains long-term multi-lineage human hematopoiesis and is capable of mounting immune responses. Thus, this model shows considerable promise to study long-term in vivo HIV infection and pathogenesis. RESULTS: Here we demonstrate that RAG-hu mice produce human cell types permissive to HIV-1 infection and that they can be productively infected by HIV-1 ex vivo. To assess the capacity of these mice to sustain long-term infection in vivo, they were infected by either X4-tropic or R5-tropic HIV-1. Viral infection was assessed by PCR, co-culture, and in situ hybridization. Our results show that both X4 and R5 viruses are capable of infecting RAG-hu mice and that viremia lasts for at least 30 weeks. Moreover, HIV-1 infection leads to CD4 T cell depletion in peripheral blood and thymus, thus mimicking key aspects of HIV-1 pathogenesis. Additionally, a chimeric HIV-1 NL4-3 virus expressing a GFP reporter, although capable of causing viremia, failed to show CD4 T cell depletion possibly due to attenuation. CONCLUSION: The humanized RAG-hu mouse model, characterized by its capacity for sustained multi-lineage human hematopoiesis and immune response, can support productive HIV-1 infection. Both T cell and macrophage tropic HIV-1 strains can cause persistent infection of RAG-hu mice resulting in CD4 T cell loss. Prolonged viremia in the context of CD4 T cell depletion seen in this model mirrors the main features of HIV infection in the human. Thus, the RAG-hu mouse model of HIV-1 infection shows great promise for future in vivo pathogenesis studies, evaluation of new drug treatments, vaccines and novel gene therapy strategies.

Animals↗
PubMed2006

Amelioration of amyloid load by anti-Abeta single-chain antibody in Alzheimer mouse model.

Parenteral immunization of transgenic mouse models of Alzheimer disease (AD) with synthetic amyloid beta-peptide (Abeta) prevented or reduced Abeta deposits and attenuated their memory and learning deficits. A clinical trial of immunization with synthetic Abeta, however, was halted due to brain inflammation, presumably induced by a toxic Abeta, T-cell- and/or Fc-mediated immune response. Another issue relating to such immunizations is that some AD patients may not be able to raise an adequate immune response to Abeta vaccination due to immunological tolerance or age-associated decline. Because peripheral administration of antibodies against Abeta also induced clearance of amyloid plaques in the model mice, injection of humanized Abeta antibodies has been proposed as a possible therapy for AD. By screening a human single-chain antibody (scFv) library for Abeta immunoreactivity, we have isolated a scFv that specifically reacts with oligomeric Abeta as well as amyloid plaques in the brain. The scFv inhibited Abeta amyloid fibril formation and Abeta-mediated cytotoxicity in vitro. We have tested the efficacy of the human scFv in a mouse model of AD (Tg2576 mice). Relative to control mice, injections of the scFv into the brain of Tg2576 mice reduced Abeta deposits. Because scFvs lack the Fc portion of the immunoglobulin molecule, human scFvs against Abeta may be useful to treat AD patients without eliciting brain inflammation.

Alzheimer Disease↗
PubMed2006

Effects of systemic and local administration of recombinant human IGF-I (rhIGF-I) on de novo bone formation in an aged mouse model.

UNLABELLED: DO was used in an aged mouse model to determine if systemically and/or locally administered rhIGF-I improved osteoblastogenesis and new bone formation. Local and systemic rhIGF-I treatment increased new bone formation. However, only systemic delivery produced measurable concentrations of rhIGF-I in the circulation. INTRODUCTION: Human and rodent research supports a primary role for IGF-I in bone formation. Significant roles for both endocrine and paracrine/autocrine IGF-I have been suggested for normal osteoblastogenesis and bone formation. We have assessed, using a mouse model of distraction osteogenesis (DO), the impact of continuous administration of recombinant human (rh)IGF-I, delivered either locally to the distraction site or absorbed systemically, on bone formation in an aged mouse model. MATERIALS AND METHODS: DO was performed in aged mice (18-month-old C57BL/6 male mice), which were distracted at 0.15 mm daily. At the time of osteotomy, miniosmotic pumps were inserted subcutaneously to (1) deliver vehicle or rhIGF-I subcutaneously for systemic delivery or (2) deliver vehicle or rhIGF-I directly to the newly forming bone through infusion tubing routed subcutaneously from the pump to the distraction site. Serum concentrations of mouse IGF-I, human IGF-I, and osteocalcin were determined at the end of the study. RESULTS: New bone formation observed in DO gaps showed a significant increase in new bone formation in rhIGF-I-treated mice, irrespective of delivery route. However, detectable levels of human IGF-I were found only in the serum of animals receiving rhIGF-I systemically. Osteocalcin levels did not differ between controls and rhIGF-I-treated groups. CONCLUSIONS: Locally and systemically delivered rhIGF-I both produce significant increases in new bone formed in an aged mouse model in which new bone formation is normally markedly impaired, suggesting that rhIGF-I may improve senile osteoporosis. Because systemic administration of IGF-I can result in untoward side effects, including an increased risk for cancer, the findings that locally delivered IGF-I improves bone regeneration without increasing circulating IGF-I levels suggests that this delivery route may be preferable in an at-risk, aged population.

Aging↗