Mus musculus
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PROVIDER: PRJNA91143 | ENA |
REPOSITORIES: ENA
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Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.
| S-EPMC11335981 | biostudies-literature
Project description:SUMMARY; Medulloblastoma is the most common malignant brain tumor in children. It is thought to result from transformation of granule cell precursors (GCPs) in the developing cerebellum, but little is known about the early stages of the disease. Here we identify a pre-neoplastic stage of medulloblastoma in patched heterozygous mice, a model of the human disease. We show that pre-neoplastic cells are present in the majority of patched mutants, although only 16% of these mice develop tumors. Pre-neoplastic cells, like tumor cells, exhibit activation of the Sonic hedgehog pathway and constitutive proliferation. Importantly, they also lack expression of the wild-type patched allele, suggesting that loss of patched is an early event in tumorigenesis. While pre-neoplastic cells resemble GCPs and tumor cells in many respects, they have a distinct molecular signature. Genes that mark the pre-neoplastic stage include regulators of migration, apoptosis and differentiation, processes critical for normal development but previously unrecognized for their role in medulloblastoma. The identification and molecular characterization of pre-neoplastic cells provides insight into the early steps in medulloblastoma formation, and may yield important markers for early detection and therapy of this disease. ANIMALS; Patched heterozygous mice (Goodrich et al., 1997) were obtained from Matthew Scott's lab at Stanford, and maintained by breeding with 129X1/SvJ mice from Jackson Laboratories. Math1-GFP transgenic mice (Lumpkin et al., 2003) were provided by Jane Johnson at UT Southwestern Medical Center. Math1-GFP/patched+/- mice were generated by crossing patched heterozygotes with Math1-GFP mice, and then backcrossing to Math1-GFP mice three times before further analysis. All mice were maintained in the Cancer Center Isolation Facility at Duke University Medical Center. ISOLATION OF CELLS; Granule cell precursors (GCPs) were isolated from 7-day-old (P7) patched+/- mice; preneoplastic cells were obtained from 6 week-old patched mutants; and tumor cells were obtained from 10-25-week old patched mutants displaying physical and behavioral signs of medulloblastoma. Cells were isolated from each source using a protocol described in (Wechsler- Reya and Scott, 1999). Briefly, cerebella were digested in solution containing 10 U/ml papain Oliver et al. Pre-Neoplastic Stage of Medulloblastoma - 8 - (Worthington, Lakewood, NJ) and 250 U/ml DNase (Sigma) and triturated to obtain a cell suspension. This suspension was centrifuged through a step gradient of 35% and 65% Percoll (Amersham Biosciences, Piscataway, NJ), and cells were harvested from the 35%-65% interface. Cells were resuspended in serum-free culture medium consisting of Neurobasal containing B27 supplement, sodium pyruvate, L-glutamine, and penicillin/streptomycin (all from Invitrogen, Carlsbad, California) and counted on a hemacytometer. Cells used for RNA isolation were centrifuged and flash frozen in liquid nitrogen. For proliferation assays or immunostaining, cells were plated on poly-D-lysine (PDL)-coated tissue culture vessels and incubated in serum-free culture medium. MICROARRAY HYBRIDIZATION AND ANALYSIS; RNA from GCPs, pre-neoplastic cells and tumor cells (isolated as described above, but not FACS-sorted) and from normal adult cerebellum (not dissociated) was converted to cDNA using the Superscript Choice cDNA kit (Invitrogen) and a T7-dT(24) primer (Genset/Proligo, Boulder, CO). cRNA was generated using a T7-transcription/labeling kit from Enzo Life Sciences and hybridized to Affymetrix U74Av2 chips (Affymetrix, Santa Clara, CA). Chips were scanned, and hybridization data were acquired using Affymetrix Suite 5.0 software. Affymetrix CEL files were normalized and quantified using Bioconductor software with the gcRMA model to quantify gene expression levels (Gentleman and Carey, 2002). Unsupervised principal components analysis (PCA) was used to identify the relationships among normal adult cerebellum, GCPs, pre-neoplastic cells and tumor cells based on expression profiles. To identify genes that were differentially expressed among GCPs, pre-neoplastic cells and tumor cells, supervised analysis was carried out. A gene-by-gene ANOVA model with three groups (GCP, pre-neoplastic, tumor) was used to fit the log2-transformed intensities. To correct for multiple comparisons, the nominal p-value was adjusted using the false discovery rate (Benjamini and Hochberg, 1995). Genes were considered to be differentially expressed if they satisfied all of the following criteria: a difference in expression greater than 1.9-fold between any two groups, a maximum absolute intensity difference larger than 32 units, and an adjusted pvalue < 0.01. There were 118 genes that met these criteria. The identities of differentially expressed genes were verified by integrating data from the Affymetrix and Unigene databases. Gene functions were determined using information from Gene Ontology, Unigene, LocusLink and PubMed databases. Clustering was performed with Cluster and Treeview (Eisen et al., 1998). All statistical analysis was performed using R-1.7 software (Dalgaard, 2002). Results were visualized with Spotfire 6.0 (Somerville, MA). CORRESPONDING AUTHOR; Robert J. Wechsler-Reya*; Dept. of Pharmacology & Cancer Biology,; Duke University Medical Center Box 3813, Durham, NC 27710; Phone: 919-613-8754. Fax: 919-668-3556. Email: rw.reya@duke.edu; SUBMITTER_CITATION: Oliver TG, Read TA. Kessler JS, Mehmeti A, Wekks JF, Huynh TT, Lin SM, Wechsler-Reya RJ, Loss of patched and disruption of granule cell development in a pre-neoplastic stage of medulloblastoma, Development, 132, 2425-2439 (2005)
2007-08-31 | E-GEOD-2426 | biostudies-arrayexpress
Project description:BACKGROUND: Long terminal repeat (LTR) retrotransposons make up a large fraction of the typical mammalian genome. They comprise about 8% of the human genome and approximately 10% of the mouse genome. On account of their abundance, LTR retrotransposons are believed to hold major significance for genome structure and function. Recent advances in genome sequencing of a variety of model organisms has provided an unprecedented opportunity to evaluate better the diversity of LTR retrotransposons resident in eukaryotic genomes. RESULTS: Using a new data-mining program, LTR_STRUC, in conjunction with conventional techniques, we have mined the GenBank mouse (Mus musculus) database and the more complete Ensembl mouse dataset for LTR retrotransposons. We report here that the M. musculus genome contains at least 21 separate families of LTR retrotransposons; 13 of these families are described here for the first time. CONCLUSIONS: All families of mouse LTR retrotransposons are members of the gypsy-like superfamily of retroviral-like elements. Several different families of unrelated non-autonomous elements were identified, suggesting that the evolution of non-autonomy may be a common event. High sequence similarity between several LTR retrotransposons identified in this study and those found in distantly-related species suggests that horizontal transfer has been a significant factor in the evolution of mouse LTR retrotransposons.
| S-EPMC395764 | biostudies-literature
Project description:BackgroundCopy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously.ResultsWe found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of CNV uniqueness (single sample occurrence) and the nature of CNV-gene overlap between wild-caught mice and classical laboratory strains. CNV-gene overlap was associated with lipid metabolism, pheromone response and olfaction compared to immunity, carbohydrate metabolism and amino-acid metabolism for wild-caught mice and classical laboratory strains, respectively. Using two subspecies of wild-caught Mus musculus, we identified putative CNVs unique to those subspecies and show this diversity is better captured by wild-derived laboratory strains than by the classical laboratory strains. A total of 9 genic copy number variable regions (CNVRs) were selected for experimental confirmation by droplet digital PCR (ddPCR).ConclusionThe analysis we present is a comprehensive, genome-wide analysis of CNVs in Mus musculus, which increases the number of known variants in the species and will accelerate the identification of novel variants in future studies.
| S-EPMC4490682 | biostudies-literature
Project description:House mice (Mus musculus) emit ultrasonic vocalizations (USVs), which are surprisingly complex and have features of bird song, but their functions are not well understood. Previous studies have reported mixed evidence on whether there are sex differences in USV emission, though vocalization rate or other features may depend upon whether potential receivers are of the same or opposite sex. We recorded the USVs of wild-derived adult house mice (F1 of wild-caught Mus musculus musculus), and we compared the vocalizations of males and females in response to a stimulus mouse of the same- or opposite-sex. To detect and quantify vocalizations, we used an algorithm that automatically detects USVs (Automatic Mouse Ultrasound Detector or A-MUD). We found high individual variation in USV emission rates (4 to 2083 elements/10 min trial) and a skewed distribution, with most mice (60%) emitting few (?50) elements. We found no differences in the rates of calling between the sexes overall, but mice of both sexes emitted vocalizations at a higher rate and higher frequencies during opposite- compared to same-sex interactions. We also observed a trend toward higher amplitudes by males when presented with a male compared to a female stimulus. Our results suggest that mice modulate the rate and frequency of vocalizations depending upon the sex of potential receivers.
| S-EPMC5728457 | biostudies-literature
Project description:PGCs undergo two distinct stages of demethylation before reaching a hypomethylated ground state at E13.5. Stage 1 occurs between E7.25- E9.5 in which PGCs experience a global loss of cytosine methylation. However, discreet loci escape this global loss of methylation and between E10.5-E13.5, stage 2 of demethylation takes place. In this stage these loci are targeted by Tet1 and Tet2 leading to the loss of the remaining methylation and resulting in the epigenetic ground state. Our data shows that Dnmt1 is responsible for maintaining the methylation of loci that escape stage 1 demethylation, and that it functions in a UHRF1 independent manner. Our data further demonstrates that when these loci lose methylation prior to stage 2 it results in early activation of the meiotic program, which leads to precocious differentiation of the germ line resulting in a decreased pool of PGCs in the embryo and subsequent infertility in adult mice.
2016-09-13 | GSE74938 | GEO
Project description:The mammalian vomeronasal organ (VNO) expresses two G-protein coupled receptor gene families that mediate pheromone responses, the V1R and V2R receptor genes. In rodents, there are ~150 V1R genes comprising 12 subfamilies organized in gene clusters at multiple chromosomal locations. Previously, we showed that several of these subfamilies had been extensively modulated by gene duplications, deletions, and gene conversions around the time of the evolutionary split of the mouse and rat lineages, consistent with the hypothesis that V1R repertoires might be involved in reinforcing speciation events. Here, we generated genome sequence for one large cluster containing two V1R subfamilies in Mus spretus, a closely related and sympatric species to Mus musculus, and investigated evolutionary change in these repertoires along the two mouse lineages.We describe a comparison of spretus and musculus with respect to genome organization and synteny, as well as V1R gene content and phylogeny, with reference to previous observations made between mouse and rat. Unlike the mouse-rat comparisons, synteny seems to be largely conserved between the two mouse species. Disruption of local synteny is generally associated with differences in repeat content, although these differences appear to arise more from deletion than new integrations. Even though unambiguous V1R orthology is evident, we observe dynamic modulation of the functional repertoires, with two of seven V1Rb and one of eleven V1Ra genes lost in spretus, two V1Ra genes becoming pseudogenes in musculus, two additional orthologous pairs apparently subject to strong adaptive selection, and another divergent orthologous pair that apparently was subjected to gene conversion.Therefore, eight of the 18 (~44%) presumptive V1Ra/V1Rb genes in the musculus-spretus ancestor appear to have undergone functional modulation since these two species diverged. As compared to the rat-mouse split, where modulation is evident by independent expansions of these two V1R subfamilies, divergence between musculus and spretus has arisen more by mutations within coding sequences. These results support the hypothesis that adaptive changes in functional V1R repertoires contribute to the delineation of very closely related species.
| S-EPMC2644715 | biostudies-literature
Project description:Rodent betaherpesviruses vary considerably in genomic content, and these variations can result in a distinct pathogenicity. Therefore, the identification of unknown betaherpesviruses in house mice (Mus musculus), the most important rodent host species in basic research, is of importance. During a search for novel herpesviruses in house mice using herpesvirus consensus PCR and attempts to isolate viruses in tissue culture, we identified a previously unknown betaherpesvirus. The primary PCR search in mouse organs revealed the presence of known strains of murine cytomegalovirus (Murid herpesvirus 1) and of Mus musculus rhadinovirus 1 only. However, the novel virus was detected after incubation of organ pieces in fibroblast tissue culture and subsequent PCR analysis of the supernatants. Long-distance PCR amplification including the DNA polymerase and glycoprotein B genes revealed a 3.4 kb sequence that was similar to sequences of rodent cytomegaloviruses. Pairwise sequence comparisons and phylogenetic analyses showed that this newly identified murine virus is most similar to the English isolate of rat cytomegalovirus, thereby raising the possibility that two distinct CMV lineages have evolved in both Mus musculus and Rattus norvegicus.
| S-EPMC2804612 | biostudies-literature