PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Mice, Mutant Strains”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 163 records · Page 9Linked to original sources
PubMed1993

Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice.

We describe the spontaneous development of inflammatory bowel disease (IBD) in several immunodeficient mouse strains created via gene targeting in embryonic stem cells. Chronic colitis was observed in T cell receptor (TCR) alpha mutant, TCR beta mutant, TCR beta x delta double mutant, or class II major histocompatibility complex (MHC) mutant mice, but not in recombination-activating gene RAG-1 mutant mice or nude mice kept in the same specific pathogen-free animal facility. This clinical pattern suggests that the disease requires the presence of B lymphocytes and the absence of class II MHC-restricted CD4+ alpha beta T cells. IBD in the mutant mice has some of the features of the human disease ulcerative colitis. Based on these results, we suggest that dysfunction of the mucosal immune system may underly the pathogenesis of some types of IBD in humans.

Aging↗
PubMedDate not supplied

Mechanisms of hormone-mediated carcinogenesis of the ovary.

Experimental ovarian carcinogenesis has been investigated in inbred and hybrid strains of mice and induced by a diversity of mechanisms including X-irradiation, oocytotoxic xenobiotic chemicals, ovarian grafting to ectopic or orthotopic sites, neonatal thymectomy, mutant genes reducing germ cell populations, and aging. Disruptions in the function of graafian follicles by a variety of mechanisms results in a spectrum of ovarian proliferative lesions, including tumors. The findings in mutant and genetically engineered mice support the concept of a secondary (hormonally mediated) mechanism of ovarian tumorigenesis in mice associated with sterility. Multiple pathogenic factors that either destroy or diminish the numbers of graafian follicles in the ovary result in decreased sex hormone secretion, especially estradiol-17beta, leading to a compensatory overproduction of pituitary gonadotrophins, particularly LH, which places the mouse ovary at an increased risk for developing tumors in chronic studies. The intense proliferation of ovarian surface epithelium and stromal (interstitial) cells with the development of unique tubular adenomas in response to sterility does not appear to have a counterpart in the ovaries of adult human females.

Animals↗
PubMed2006

Phenotypic analysis of the mouse placenta.

Placental development is a dynamic and complex process and much of our current understanding of the underlying molecular processes comes from analysis of targeted gene mutations in mice. There are more than 50 strains of mutant mice that have placental defects, and it has become widely appreciated that placental defects should be suspected in cases where embryonic lethality is observed. The degree to which these phenotypes are investigated is highly variable, owing to a general lack of expertise in the field. However, there has been considerable progress in developing techniques and reagents for analyzing placental phenotypes that are relatively simple to apply and that should be accessible to all investigators. This chapter provides a basic outline of the strategies for the general identification and then the subsequent detailed investigation of placental phenotypes.

Alkaline Phosphatase↗
PubMed2002

Response of the phiX174 am3, cs70 transgene to acute and chronic ENU exposure: implications for protocol design.

Studies of other transgenic assays have shown that time after treatment is a very important variable in the analysis of mutation frequencies but that eventually a plateau frequency is reached, indicating that the mutations are neutral. This neutrality is very important for the design of both experiments and testing protocols. Here we show that the phiX174 am3, cs70 transgene gives qualitatively similar results to the other transgenes studied after exposure of the mice to N-ethyl-N-nitrosourea. In the small intestine, the mutant frequency induced by an acute dose did not change significantly from 10 to 70 days post-treatment, indicating that the mutations induced are, indeed, neutral. Likewise, the mutant frequency increased linearly with duration of exposure to ENU at a constant rate. Mutant frequencies obtained were 10 times higher from the chronic exposure than produced by a nearly lethal acute dose. As in previous comparisons of a transgene and the endogenous Dlb-1 locus in the small intestine, the chronic exposure was much more effective at increasing the sensitivity of the transgene than of the endogenous gene. The Dlb-1 locus shows more complex kinetics in this strain, as in others, with mutations initially accumulating at a slower rate, indicating a differential repair of genetic damage.

Animals↗
PubMed2004

Transgenic analysis of scleroderma: understanding key pathogenic events in vivo.

Modern molecular genetic methods have allowed better understanding of established mouse models of scleroderma and also facilitated the development of new and better defined mouse strains for investigating the pathogenesis of the disease. The best characterized scleroderma animal model is the type 1 tight skin mouse (Tsk1). Backcrossing these animals with other mutant strains has been informative. These experiments implicate the IL-4 ligand-receptor axis in the development of skin fibrosis. Parallel expression analysis of genes using microarrays has provided insight into novel mediators of fibrosis including the C-C chemokine MCP-3. Other experiments suggest that embryonically defined fibroblast-specific regulatory elements may be targets for activation in this model. The same lineage-specific elements have been used to selectively activate TGF beta signaling pathways in fibrosis to generate a novel model for scleroderma and also have been used to develop systems for ligand-dependent fibroblast-specific genetic recombination that will allow further analysis key candidate genes implicated in scleroderma pathogenesis. Better mouse models will improve understanding of this intractable rheumatic disease and can be expected to ultimately lead to improved treatments and outcome.

Animals↗
PubMed2004

Strain-dependent inhibitory effect of mutant mi-MITF on cytotoxic activities of cultured mast cells and natural killer cells of mice.

MITF is a transcription factor encoded by the mi locus. MITF encoded by mi and Mi(or) mutant alleles (mi-MITF and Mi(or)-MITF, respectively) possessed an inhibitory effect, whereas the tg, mi(ew) and mi(ce) were null mutants. We examined the cytotoxic activities of cultured mast cells (CMCs) and natural killer (NK) cells of various MITF mutants in C57BL/6 (B6) background. Cytotoxic activities of CMCs and NK cells of B6-mi/mi and B6-Mi(or)/Mi(or) mice were remarkably reduced. In B6-tg/tg, B6-mi(ew)/mi(ew) and B6-mi(ce)/mi(ce) mice, however, the cytotoxic activity of CMCs was reduced only slightly and the NK activity was normal. The cytotoxic activity of CMCs paralleled with the expression level of granzyme B (Gr B) mRNA, and the NK activity with that of perforin (Pfn) mRNA. In contrast to the case of B6-mi/mi mice, cytotoxic activities of CMCs and NK cells were not impaired in WB-mi/mi mice. The expression of Gr B mRNA was not reduced in CMCs of WB-mi/mi mice, and that of Pfn mRNA was not reduced in NK cells of WB-mi/mi mice. WB-mi/mi mice appeared to have factor(s) compensating for the inhibitory effect of mi-MITF on the expression of Gr B and Pfn genes.

Animals↗
PubMed1988

Partial suppression of anchorage-independent growth and tumorigenicity in immunodeficient mice by transfection of the H-2 class I gene H-2Ld into a human colon cancer cell line (HCT).

Many human tumors, particularly those of epithelial origin, appear to express greatly reduced levels of major histocompatibility complex class I antigens on their surface. It has been previously reported that the class I gene H-2Ld, introduced into adenovirus type 12-transformed mouse cells, induces reversal of oncogenesis in immunocompetent BALB/c mice. We have tested the hypothesis that the H-2Ld gene, when transfected into HCT colon cancer cells, may alter their transformed phenotype. Two H-2Ld transfectants, HCT-Ii and HCT-If, were found to exhibit a markedly reduced-to-virtually suppressed ability to form colonies in soft agar in comparison to a transfectant (HCTh) carrying only the neomycin-resistance gene. We also compared the tumorigenicity of HCTh vs. HCT-If cells in two different strains of immunodeficient mice: nude (T-) and triple-deficient mutants (T-, NK-, B-). At 28 days postinjection of 10(7) and 10(6) cells, the size and growth rate of HCT-If tumors were greatly reduced compared to HCTh cells. Therefore, as assayed in immunodeficient animals, expression of the class I H-2Ld gene in HCT cells appears to correlate with partial suppression of the tumorigenic phenotype, suggesting that the expression of a transfected class I gene may by itself alter the phenotype of the recipient cell and that such phenotypic changes may be independent of the immune system.

Animals↗
PubMed1995

The segment-specific pattern of A-raf expression in the mouse epididymis is regulated by testicular factors.

The protooncogene homolog A-raf is expressed at high levels in a variety of steroid-responsive tissues and exhibits a highly regionalized pattern of expression in morphologically and functionally distinct segments of the mouse epididymis: the highest levels occur in the proximal caput, lower levels occur in the initial segment, and intermediate levels are found in the distal caput. Castration abolished detectable A-raf expression throughout the epididymis. The administration of exogenous androgens restored expression to precastrate levels, indicating that circulating, rather than intraluminal, levels of androgens are sufficient to maintain expression. Although overall levels of A-raf were maintained in androgen-replaced animals, the segment-specific pattern of expression was altered. Elevated levels of A-raf were expressed in the initial segment relative to those in controls. Coincident with this, the morphology of the epithelial cells in the initial segment of androgen-replaced castrates was altered to more closely resemble the morphology of proximal caput epithelial cells in controls. Similar increases in A-raf expression and changes in epithelial cell morphology relative to those in controls were observed in the initial segments of the castrate-side epididymis of hemicastrate mice, in epididymis from a germ cell-deficient strain of mutant mice, and in epididymis from intact mice supplemented with exogenous testosterone. These studies indicated that testicular products, such as spermatozoa, or substances that require germ cells for their production in the testis modulate the androgen-dependent expression of A-raf in the initial segment of the caput epididymis.

Androgen-Binding Protein↗
PubMedDate not supplied

[Study of diabetogenic and lympholytic effects during single and fractional administration of streptozotocin to mice of the mutant strain C57BL/KsIY-db/m].

Single administration of streptozotocin at a dose of 200 mg/kg into mice males of the C57BL/KsJY db/m strain induced severe form of insulin-dependent diabetes within the earlier periods as compared with fractional injection of the drug (40 mg/kg daily within 5 days). Streptozotocin-induced diabetes, developed after single administration of the drug, caused pronounced destructions in lymphoid tissue, primarily in thymus as content of DNA was drastically decreased in the tissue and level of DNA breakdown products was increased. The lympholytic effect of streptozotocin was less distinct after fractional administration.

Animals↗
PubMed1996

New insights into the regulation of somatotrope function using genetic and transgenic models.

Growth hormone (GH) secretion is under the control of the hypothalamic hormones GH-releasing hormone (GHRH) and somatostatin (SRIF), and is regulated by feedback effects of GH and insulin-like growth factor (IGF-1). GHRH and SRIF act on somatotropes by binding to G-protein-coupled receptors. GHRH activates the stimulatory G protein (Gs), leading primarily to activation of adenylyl cyclase and protein kinase A. SRIF activates the inhibitory G protein (Gi). Several animal models enable the study of various disorders of GH secretion in vivo. Genetic models of impaired GH secretion include the little (lit) mouse, the dwarf (dw) rat, the fatty (fa) rat, and the high-growth (hg) mouse. Transgenic models of impaired and excessive GH secretion, respectively, include the tyrosine hydroxylase-human GH (TH-hGH) transgenic mouse and the metallothionein-human GHRH transgenic mouse. These models encompass a wide spectrum of disorders of GH secretion, involving defects of hypothalamic regulation, feedback control at the pituitary level, or the mechanism of GHRH action in the somatotrope. They may provide insights into our understanding of human GH secretory disorders.

Animals↗
PubMed2000

Phenotype assessment: are you missing something?

BACKGROUND AND PURPOSE: Phenotype assessment of genetically modified rodents is an essential component of animal model development and their eventual use. Described here is a paradigm to consider as we collectively pursue phenotype assessment of the constantly increasing number of genetically modified rodent models, as well as those with spontaneously occurring mutations. METHODS: Review of past experiences and the literature provides useful examples to illustrate the principles described. CONCLUSION: A practical approach to phenotype assessment can be divided into a primary level of assessment to find abnormalities, and a secondary level of more specialized assessment to quantify and evaluate the abnormalities detected. There are many subtle, but important phenotypic characteristics that can be markedly affected by the background genetics and environment of the animal being assessed.

Acyl-CoA Dehydrogenase↗
PubMedDate not supplied

[Cerebellar ataxia and absence epilepsy: genes, channels, neurons and mice].

AIMS: To briefly review the most significant progress made in the fields of molecular genetics and cellular electrophysiology that have contributed to reveal that some paroxysmal disorders including epilepsy, are linked to voltage gated Ca2+ (CaV) channel abnormalities. DEVELOPMENT: Recent studies showed that the gene encoding the P/Q type Ca2+ channel is altered in a number of mutant mice strains. Phenotypic alterations of these mice include cerebellar dysfunction and absence epilepsy. CONCLUSIONS: These mutant mice offer a unique opportunity to elucidate the molecular, developmental, and physiological mechanisms underlying CaV channel activity in the brain, and provide the possibility to link specific CaV channel subunits to cellular disease processes, including altered excitability, synaptic signaling, and cell death.

Animals↗
PubMed1990

Serological and histological characterization of the new mutant strain of lpr mice, CBA/KlJms-lprcg/lprcg.

CBA/KlJms-lprcg/lprcg mice with a novel mutation producing systemic lymphoproliferation were investigated for their serological and histological characteristics. The mutant mice showed elevated levels of serum immunoglobulin, C1q-binding immune complexes and antibodies to nuclear antigens such as dsDNA and ssDNA and poly(ADP-ribose). In contrast, histopathological lesions, e.g. glomerulonephritis, vasculitis or interstitial pneumonitis, were not revealed by histological and immunofluorescent examinations, except for lymphocytic infiltration in various organs. These results suggest that this mutant mouse strain may provide a new animal model for autoimmunity. However, further investigations are required to clarify whether this strain is unique as compared with other well-known lupus-prone strains of mice with respect to serological and histological abnormalities and become to be a new model of systemic autoimmune disease.

Animals↗
PubMed1991

A new mouse strain manifesting high proteinuria and kidney glomerular defect.

A mutant strain of mice manifesting high proteinuria, wasting syndrome, and kidney glomerular defect was established from the F5 offspring of an interstrain cross of CBA/Nga and RFM/Nga mice. Affected mice had high levels of proteinuria after 40 days of age. The body weight of about 22.6% of affected mice decreased rapidly and they died between 3 and 5 months of age. We learned that this abnormality is controlled by two pairs of autosomal recessive genes; the mutant strain of mice is designated FGS/Nga. The mutant strain has been characterized by high proteinuria and renal lesions with focal sclerosis of glomeruli and tubular atrophy with interstitial nephritis in the kidney resembling the human disease. The FGS/Nga mouse strain is a potential animal model for studying kidney glomerular defect in humans.

Animals↗
PubMed2006

Age-related changes in the motricity of the inbred mice strains 129/sv and C57BL/6j.

The development of motor skills was studied at different stages in the life of the mouse, focusing on three key aspects of motor development: early rhythmic motor activities prior to the acquisition of quadruped locomotion, motor skills in young adults, and the effect of aging on motor skills. The age-related development pattern was analysed and compared in two strains of major importance for genomic studies (C57Bl6/j and 129/sv). Early rhythmic air-stepping activities by l-dopa injected mice showed similar overall development in both strains; differences were observed with greater beating frequency and less inter-limb coordination in 129/sv, suggesting that 129/sv had a different maturation process. Performance on the rotarod by young adult C57Bl6/j gradually improved between 1 and 3 months, but then declined with age; performance on the treadmill also declined with an age-related increase in fatigability. Overall performance by 129/sv mice was lower than C57Bl6/j, and the age-related pattern of change was different, with 129/sv having relatively stable performance over time. Inter-strain differences and their possible causes, in particular the role of dopaminergic pathways, are discussed together with repercussions affecting mutant phenotyping procedures.

Aging↗
PubMed2001

[The use of mutagenic and transgenic mice for the study of aging mechanisms and age pathology].

Increased interest is emerging for using mouse models to assess the genetics of aging and age-related diseases, cancer including. Despite this demand, relatively little information is available on relations between aging and spontaneous tumor development in transgenic and null mutant mice. Analysis of various transgenic and knockout rodent models which characterized by shortening or extension of the life span gives an unique possibility to evaluate the role of involved in aging genes in mechanisms of carcinogenesis. Only few models represent examples of life span extension. Ames dwarf mutant mice, p66-/- knocked out mice, aMUPA and MGMT, transgenic mice live longer than wild-type strains. The incidence of spontaneous tumors in these mice was usually similar to those in controls, whereas the latent period of tumor development was increased. Practically all models of accelerated aging show the increased tumor incidence and shortening of tumor latency. This phenomenon has been observed both in animals which display phenotype more resemble to the natural aging and in animals showed only partial features of normal aging process. These observations are in agreement with the data on the positive correlation between tumor incidence and the rate of its age-related increase, and the aging rate in a population.

Age Factors↗
PubMed1999

The H-mshi antigen is conserved among standard BALB/cBy, C57BL/6J, and wild-derived CAST/Ei and SPRET/Ei inbred strains of mice.

The recessive male sterility and histoincompatibility mutation (mshi) arose spontaneously in the standard inbred mouse strain BALB/cBy. In addition to generating sterility in homozygous males, mshi controls the loss of a minor histocompatibility antigen designated H-mshi. To determine whether the H-mshi antigen normally expressed by the BALB/cBy strain (H-mshi(c)) is the same as or different from the antigen (H-mshi(x)) expressed by the standard inbred C57BL/6J strain or the wild-derived CAST/Ei and SPRET/Ei strains, animals heterozygous for the mutant antigen-loss allele (H-mshi-) and H-mshi(x) were grafted with tail skin from BALB/cBy mice. The long-term retention of grafts by these hosts indicates that the H-mshi antigen encoded by the BALB/cBy, C57BL/6J, CAST/Ei, and SPRET/Ei strains is histogenically identical. Conservation of this minor histocompatibility antigen among these evolutionarily diverse strains suggests that H-mshi encodes a functionally important cellular product(s).

Animals↗