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At least 145 records · Page 8Linked to original sources
PubMed1987

Steroid receptors and human endometrial carcinoma: studies in a nude mouse model.

An experimental nude mouse system where human endometrial carcinomas of different histologic grade and steroid receptor characteristics can be grown and maintained under defined hormonal milieu by serial transplantation has been developed. Biologically and clinically important information on the role of steroid receptors in eliciting hormonal responses in these tumors has been obtained using this model. These results form the basis for designing and testing various treatment strategies for endometrial carcinomas of different histologic grade and receptor content.

Animals↗
PubMed1993

A mouse model for varicella-zoster virus latency.

Following primary infection with varicella-zoster virus (VZV), the virus establishes a latent infection in humans. The molecular pathogenesis of VZV latency is not well understood, mainly due to the lack of an adequate animal model. We report here that we have developed a mouse model for VZV infection that involves corneal inoculation of mice. Although infected animals showed no signs of disease, most of the animals could not eliminate the virus early after infection. By PCR, we demonstrated that at 33 days post-infection (p.i.), viral DNA was still present in more than 60% of the animals (14/21). VZV DNA was most frequently detected in the trigeminal ganglia (7/14) followed by the brain stem (10/21), kidneys (4/21), spleen (3/20), liver (2/21) and brain (1/21). By in situ hybridization, a few cells positive for VZV mRNA were detected in the trigeminal ganglia, brain stem, cerebellum and spleen of a small number of the infected animals as late as 33 days p.i. No viral proteins were detected at the site of inoculation or in any other tissue by immunostaining. Our results suggest that VZV spreads in mice by both viraemia and axonal transport and establishes a non-productive (latent) infection.

Animals↗
PubMed2025

Tracking HIV persistence across T cell lineages during early ART-treated HIV-1-infection using a reservoir-marking humanized mouse model.

Human immunodeficiency virus (HIV) infection depletes CD4 T-cells, and long-term persistence of latent virus prevents full clearance of HIV even in the presence of effective antiretroviral therapy (ART), Here we present the HIV-1-induced lineage tracing (HILT) system, a model that irreversibly marks infected cells within a humanized mouse model, which detects rare latently infected cells. Immunodeficient mice transplanted with genetically modified hematopoietic stem cells develop a human immune system, in which CD4 T-cells contain a genetic switch that permanently labels cells infected by HIV-1 expressing cre-recombinase. Through single-cell RNA sequencing of HILT-marked cells during acute infection and post-ART treatment, we identify distinct CD4+ T-cell transcriptional lineages enriched in either active or latent infections. Comparative gene expression analysis highlights common pathways modulated in both states, including EIF2, Sirtuin, and protein ubiquitination. Critical regulators of these pathways, including JUN, BCL2, and MDM2, change to opposite directions in the two states, highlighting gene expression programs that may support HIV persistence across T-cell lineages and states.

Animals↗
PubMed2026

A mouse model of autosomal dominant spastic ataxia and myopathy caused by a mutation in Tuba4a.

Hereditary ataxias are a heterogeneous group of neurodegenerative disorders characterized by impaired balance and coordination, often due to cerebellar dysfunction. Despite advances in identifying genetic causes, animal models remain essential for dissecting underlying mechanisms and testing therapeutic strategies. Here we describe a mouse model of spastic ataxia and myopathy caused by a missense mutation in Tuba4a (n.A626C, p.Gln176Pro). In an ENU mutagenesis screen, a male C57BL/6 J mouse exhibiting muscle wasting and an intention tremor starting at approximately 4 weeks-of-age was identified. The male was bred by in vitro fertilization to BALB/cByJ oocyte donors. Genetic mapping determined dominant inheritance and localized the mutation to Chromosome 1. Genome sequencing revealed single nucleotide polymorphisms (SNPs) in serine threonine kinase 36 (Stk36Y1003N) and alpha-tubulin 4A (Tuba4aQ176P) in the mapping interval. These SNPs were CRISPR-engineered into C57BL/6 J mice, which confirmed the Tuba4aQ176P variant as the causative mutation. Mutant mice are normal at 3 weeks, except for decrement in muscle response following repetitive nerve stimulation. However, by 30 days these mice have overt ataxia, Purkinje neuron degeneration, and extensive skeletal muscle defects, which contribute to a decreased lifespan. Dominant TUBA4A mutations in humans are associated with spastic ataxia type 11 (SPAX11), congenital myopathy type 26 (CMYO26), and frontotemporal dementia/amyotrophic lateral sclerosis type 9 (FTDALS9). Our mice exhibit hallmark features of SPAX11 and CMYO26, but do not show motor neuron degeneration. This specificity makes this model a valuable tool for studying cell-type selective effects of TUBA4A mutations in neurodegeneration and myopathy.

Animals↗
PubMed1994

Herpes simplex virus encephalitis in a mouse model: PCR evidence for CNS latency following acute infection.

We have used a mouse model of herpes simplex encephalitis produced by intranasal inoculation of virus to study the expression of viral immediate early, early and late genes and latency associated transcript (LAT) in trigeminal ganglia and brain at various times after inoculation. A PCR technique was used to detect the viral gene transcripts. All viral genes were expressed between post-inoculation days 1 and 13. On post-inoculation day 42 when the acute infection had subsided only the LAT could be detected, most commonly (70%) in the trigeminal ganglion but also, in 50% of mice, in the brain stem, in 40% in olfactory bulbs and in 20% in cerebrum and cerebellum. These findings suggest that latent infection by HSV-1 may be relatively readily established in the CNS as well as in sensory ganglia. The frequency of establishment of latency appears to be related to the neuroanatomical accessibility of each brain region to the site of entry of the virus.

Animals↗
PubMed1981

Phenytoin-induced teratogenesis: a mouse model.

Malformations associated with the fetal hydantoin syndrome have been reproduced in a mouse model. The occurrence of these defects was correlated with maternal serum concentrations, but not with maternal or fetal genotype or the presence of a seizure disorder.

Animals↗
PubMed1994

Putative anticryptosporidial agents tested with an immunodeficient mouse model.

Lasalocid, sinefungin, and dehydroepiandrosterone were tested for anticryptosporidial activity with an immunodeficient mouse model at doses that have been reported effective when tested with immunosuppressed rodent models. Small but significant reductions in oocyst excretion were only observed under some conditions with lasalocid and dehydroepiandrosterone, but sinefungin had no effect.

Adenosine↗
PubMed1991

Role of influenza B virus in hepatic steatosis and mitochondrial abnormalities in a mouse model of Reye syndrome.

The hepatic steatosis observed in the influenza B virus mouse model of Reye syndrome has been attributed to infectious virus or, alternately, to decreased food intake in the virus-treated mice or impurities in the virus preparation. To resolve this issue, 4- to 6-wk-old male Balb C mice were given, by intravenous injection, 12,800 hemagglutination units of influenza B Lee/40 virus in phosphate buffered saline/1% bovine serum albumin using virus prepared by ultra-centrifugation from infected allantoic fluid, by sucrose density-gradient purification of virus prepared by ultracentrifugation from infected allantoic fluid or by irradiation of virus prepared by ultracentrifugation from infected allantoic fluid to inactivate virus. The infectivity titer of virus prepared by ultracentrifugation from infected allantoic fluid was much higher than that of sucrose density-gradient purified virus prepared from infected allantoic fluid: 50% egg infectious dose for virus prepared by ultracentrifugation from infected allantoic fluid was 3.9 x 10(4)/hemagglutination unit vs. 8.7 50% egg infectious dose/hemagglutination unit for sucrose density-gradient purified virus prepared from infected allantoic fluid. Control mice received phosphate-buffered saline/1% bovine serum albumin or uninfected allantoic fluid diluted in phosphate-buffered saline/1% bovine serum albumin. Mice were fasted to eliminate dietary variation, and livers were obtained 36 hr after virus administration. Of the above treatments, only virus prepared by ultracentrifugation from infected allantoic fluid caused clinical illness and increased hepatic triglycerides (p less than 0.02) compared with controls. Hepatic triglycerides in virus prepared by ultracentrifugation from infected allantoic fluid correlated with histopathological vacuolization scores (r = 0.5773; p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1976

Suckling mouse model for detection of heat-stable Escherichia coli enterotoxin: characteristics of the model.

Although the suckling mouse assay is widely used for the detection of heat-stable Escherichia coli enterotoxin (ST), few data have been published concerning the reproducibility, optimal growth, and test conditions of this assay. Four strains of toxigenic E. coli known to elaborate both heat-labile enterotoxin and ST or ST alone were used to study these parameters. ST activity after heat treatment and the effect of purified choleragen were also examined. ST production was optimal in Casamino Acids-yeast extract media, but both Trypticase soy and brain heart infusion broths resulted in several false negative reactions. Growing cultures in roller tubes was the most reliable method of ST production. Shaking-flask cultures and stationary-grown cultures resulted in suboptimal ST production in several strains. Optimal mouse incubation time was 3 h, and fluid secretion did not rise thereafter. Adequate toxin production occurred after 16 to 24 h of incubation. The coefficient of variation of various toxins tested on many occasions varied between 10.5 and 15.7%. Toxin activity was stable for 6 months when frozen at - 20 C. There was no decrease in ST activity when heated at 65 C for 15 min, but a small decrease was observed in two of four strains after heating at 100 C for 30 min. Choleragen, tested at various doses and at multiple times, gave uniformly negative results. These studies indicate that when done under the proper conditions, the suckling mouse assay is a simple, rapid, and reproducible assay for E. coli ST.

Animals↗
PubMed1993

Opsin synthesis in the C57BL/6-mivit/mivit mouse model of retinal degeneration.

The capacity of photoreceptor cells to synthesize opsin was evaluated in a newly-described mouse model of retinal degeneration, the C57BL/6-mivit/mivit. The mivit/mivit mouse loses photoreceptor cells at a rate of about one row per month beginning at 8 weeks, ROS are severely disrupted at 4 months, RPE is unevenly pigmented. Retinas of affected and control mice ages 4, 6, 8, 12, 16, 20, 24, 28, 32 and 52 weeks were incubated for 2 hours in medium containing [3H] leucine. Homogenates of retina samples were subjected to SDS-PAGE using disc gels. The gels were sliced and counted by scintillation. The incorporation of [3H] leucine into opsin was compared with its incorporation into other retinal proteins. During the early time points studied, mivit/mivit retinas incorporated proportionately similar amounts of [3H] leucine into opsin versus other retinal proteins as did controls. At 12 weeks, the percentage was about 80% and it continued to decline over the succeeding weeks studied. By 1 year, the proportion of leucine incorporated into opsin versus other proteins was only about 23% the amount incorporated in controls. The results of the present study suggest that the mivit/mivit photoreceptor cells are able to synthesize opsin and the gradual decline in synthetic ability follows the gradual loss of cells and is not correlated with the disruption of ROS.

Aging↗
PubMed1986

Genetic basis for a mouse model of Down syndrome.

The Trisomy 16 (Ts16) mouse has been proposed as a model for Down Syndrome (DS) in humans, based on genetic homology between mouse chromosome 16 (MMU 16) and human chromosome 21 (HSA 21). Translocations of HSA 21 resulting in trisomy for only a portion of the genetic information contained on this chromosome can result in a DS phenotype. Thus, these translocations help to define a "DS region" of the chromosome. A number of genes from this DS region of HSA 21 have been mapped to MMU 16. Techniques for localizing genes on chromosomes have been used to identify the portion of MMU 16 which corresponds to the DS region of HSA 21. This region appears to be highly conserved between mouse and human, providing further support for a mouse model of DS.

Animals↗
PubMed1987

Comparison of detection procedures for Chlamydia trachomatis, including enzyme immunoassays, in a mouse model of genital infection.

Two chlamydial enzyme immunoassays, Chlamydiazyme and IDEIA, were evaluated in a mouse model of chlamydial genital-tract infection. The Chlamydiazyme assay and the IDEIA were assessed on specimens from 10 and 11 mice, respectively. The animals were infected with Chlamydia trachomatis, strain SA2f, and the results obtained by these methods on vaginal specimens taken on 4 or 5 occasions during 41-42 days were compared with those obtained in cell culture and to a less extent by the MicroTrak direct immunofluorescence test. In comparison with culture, the Chlamydiazyme assay had a sensitivity of 62% and a specificity of 92%; IDEIA had a sensitivity of 76% and a specificity of 94%. These assays sometimes did not detect chlamydiae in specimens taken immediately before specimens which proved positive by culture and the immunoassays were less sensitive if swabs were taken after those for culture. The IDEIA also failed to detect chlamydiae in the late stage of the murine infection when chlamydial elementary bodies were seen by immunofluorescence. The implications of the observations for investigations in the human field as well as for further studies in the mouse are discussed.

Animals↗
PubMed1980

The nude mouse model for human retinoblastoma: a system for evaluation of retinoblastoma therapy.

We have critically examined the nude mouse model for human retinoblastoma to determine whether or not characteristics found in the parent tumor are retained in the mouse. We have demonstrated that most tumors grown in the anterior chamber of the nude mouse maintain a similar karyotype, show the same degree of differentiation and develop an adequate tumor blood supply when compared to the primary tumor from which they were obtained. Because of these findings, we suggest that this model may be particularly useful for evaluating new methods or combinations of treatment for human retinoblastoma.

Animals↗
PubMed1995

Calculated and TLD-based absorbed dose estimates for I-131-labeled 3F8 monoclonal antibody in a human neuroblastoma xenograft nude mouse model.

Preclinical evaluation of the therapeutic potential of radiolabeled antibodies is commonly performed in a xenografted nude mouse model. To assess therapeutic efficacy it is important to estimate the absorbed dose to the tumor and normal tissues of the nude mouse. The current study was designed to accurately measure radiation does to human neuroblastoma xenografts and normal organs in nude mice treated with I-131-labeled 3F8 monoclonal antibody (MoAb) against disialoganglioside GD2 antigen. Absorbed dose estimates were obtained using two different approaches: (1) measurement with teflon-imbedded CaSO4:Dy mini-thermoluminescent dosimeters (TLDs) and (2) calculations using mouse S-factors. The calculated total dose to tumor one week after i.v. injection of the 50 microCi I-131-3F8 MoAb was 604 cGy. The corresponding decay corrected and not corrected TLD measurements were 109 +/- 9 and 48.7 +/- 3.4 cGy respectively. The calculated to TLD-derived dose ratios for tumor ranged from 6.1 at 24 h to 5.5 at 1 week. The light output fading rate was found to depend upon the tissue type within which the TLDs were implanted. The decay rate in tumor, muscle, subcutaneous tissue and in vitro, were 9.5, 5.0, 3.7 and 0.67% per day, respectively. We have demonstrated that the type of tissue in which the TLD was implanted strongly influenced the in vivo decay of light output. Even with decay correction, a significant discrepancy was observed between MIRD-based calculated and CaSO4:Dy mini-TLD measured absorbed doses. Batch dependence, pH of the tumor or other variables associated with TLDs which are not as yet well known may account for this discrepancy.

Animals↗
PubMed1994

Sertoli cells in testes containing or lacking germ cells: a comparative study of paracrine effects using the W (c-kit) gene mutant mouse model.

BACKGROUND: Paracrine effects of germ cells on Sertoli cell structure were examined in a mouse model with the W locus (dominant white spotting) mutation in which animals with the W/Wv genotype (referred to as mutants) lack virtually all germ cells. RESULTS: Morphometric determination of Sertoli cell parameters in mutant and control (+/+) animals showed that although the testes of mutant animals were about eight times smaller than controls, the numbers of Sertoli cells in the two groups did not differ. Sertoli cell volume, Sertoli cell cytoplasmic and nuclear volumes, and Sertoli cell surface area in mutant animals were significantly smaller than in control animals. Organelle volumes and surface areas, expressed per cell, did not differ significantly in the two groups with one exception: the volume and surface area of smooth endoplasmic reticulum was significantly reduced in mutant animals. Plasma testosterone levels and tissue testosterone levels/testis were normal, indicating that the effects observed in the mutant animal were not a consequence of androgen insufficiency. Plasma FSH was elevated, probably as a consequence of germ cell depletion, and was thought not to affect Sertoli cell parameters observed. CONCLUSIONS: The data suggest that paracrine interactions with germ cells do affect Sertoli cells by modifying the amount of smooth endoplasmic reticulum. These data focus attention on the function of this abundant Sertoli cell organelle in promoting spermatogenesis.

Animals↗
PubMed1985

Qualitative and quantitative analysis of muscarinic acetylcholine receptors in the piebald lethal mouse model of Hirschsprung's disease.

Cholinergic innervation in the aganglionic bowel of the piebald lethal mouse model of Hirschsprung's disease was investigated by analysis of muscarinic acetylcholine receptors before and after administration of hexamethonium. After hexamethonium administration in the normal rectum, the maximum specific binding (Bmax) of [3H]quinuclidinyl benzilate increased from 196.6 to 346.2 fmol/mg protein without affecting the dissociation constant. This increase of muscarinic acetylcholine receptors was associated with a decrease in the 50% effective dose (ED50) of contractile response to oxotremorine from 3.8 X 10(-7) M to 6.5 X 10(-8) M. In the aganglionic rectum, hexamethonium administration did not change the Bmax (166.4 fmol/mg protein) or dissociation constant value. The ED50 of contractile response to acetylcholine and oxotremorine (4.3 X 10(-8) M, 6.5 X 10(-8) M) was lower than that in the normal rectum (1.9 X 10(-7) M, 2.0 X 10(-7) M), but it was not changed by hexamethonium. It is concluded that cholinergic innervation is congenitally absent in the aganglionic rectum in piebald lethal mice.

Acetylcholine↗
PubMed1988

A mouse model for the study of blood-brain barrier permeability.

This article describes a C57BL/6 mouse model for the investigation of blood-brain barrier (BBB) alteration. Osmotic modification of BBB was achieved by infusion of 1.6 M arabinose solution into the internal carotid artery with or without occlusion of the external carotid artery. BBB alteration was measured by infusing 2% Evans blue dye. Only 1.6 M arabinose-treated animals but not 0.9% NaCl controls displayed prominent ipsilateral staining of frontal and temporal lobes. Light blue staining occurred in animals sacrificed within 10 min after injection. Prominent staining occurred in animals sacrificed 1-6 hours later. Identically treated animals were maintained for up to 6 months without signs of systemic or neurological dysfunction. This model may permit study of the effects of biological response modifiers (BRMs) upon the central nervous system (CNS) in healthy and diseased mice.

Animals↗
PubMed1990

The sequence of changes in liver and brain in the influenza B virus mouse model of Reye's syndrome.

The time course of morphologic changes in the influenza B mouse model of Reye's syndrome is described and compared to the clinical, virologic, and biochemical changes. Following an intravenous inoculation of a lethal dose of an egg adapted strain of influenza B/Lee/40 virus, mice first showed clinical signs of lethargy and ruffled fur at 12 hours (h) post inoculation (pi). The earliest morphologic changes in the liver occurred at 12 h pi, and consisted of a slight increase in fat and loss of glycogen in hepatocytes. Over the next 36 h, the accumulation of microvesicular fat increased, and mitochondrial abnormalities such as pleomorphism and loss of dense bodies developed. There was no increase in peroxisomes. In the brain, focal cerebral edema was detected as early at 6-12 h pi. The edema, manifested as swelling of astrocytic foot processes, increased in severity with time. Endothelial cells were not abnormal. Myelin sheath splitting rarely was observed. Since changes occurred simultaneously in the liver and in the brain, we suggest that influenza B virus caused a simultaneous primary insult to both organs.

Animals↗