Mus musculus strain:Diversity Outbred
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PROVIDER: PRJNA356251 | ENA |
REPOSITORIES: ENA
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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:We measured genome-wide chromatin accessibility of embryonic stem cells derived from Diversity Outbred mice. We cultured cells in media with LIF + GSK3-beta inhibitor CHIR99021.
2020-08-13 | E-MTAB-8759 | biostudies-arrayexpress
Project description:We measured genome-wide gene expression of embryonic stem cells derived from Diversity Outbred mice. We cultured cells in media with LIF + GSK3-beta inhibitor CHIR99021. All lines were passage 3-8 when RNA was collected. We obtained RNA-Seq from technical replicate cultures for three cell lines.
2020-08-13 | E-MTAB-7728 | biostudies-arrayexpress
Project description:To understand the genetic regulation of gene expression and patterns of gene co-expression, we sequenced the transcriptome of the hippocampus of 258 Diversity Outbred (DO) mice of both sexes. DO mice (fourth and fifth generations of outcrossing) were sacrificed between 6-8 weeks of age and hippocampus dissected. Total hippocampal RNA was isolated using a TRIzol Plus RNA purification kit (Life Technologies) and mRNA sequencing library was prepared using a TruSeq kit (Illumina), both according to manufacturer's protocols. Paired-end 100bp reads were obtained using the Illumina HiSeq 2000.
2019-05-01 | E-MTAB-7637 | biostudies-arrayexpress
Project description:Clinicians and researchers are turning towards precision medicine to treat and prevent obesity and diabetes, given the known contributions of genetics to these metabolic diseases and the wide variability reported in response to treatments. Animal models that incorporate the genetic diversity present in the human population may help discover novel genetic contributors to metabolic disease and test potential treatments. We characterized the Diversity Outbred (DO) mouse population as a model in which to study interindividual variability in metabolic disease and investigated the presence of metabolic subgroups within the population. Glucose metabolism was assessed in male Diversity Outbred (DO) mice after consumption of a high-fat diet for 14 weeks and profiled transcriptomic changes in liver, adipose, and muscle—key tissues involved in glucose homeostasis. To identify metabolic subgroups, we applied classification and regression tree analyses to metabolic phenotype measures as well as transcriptomic data. These findings suggest that DO mice exhibit a diversity of metabolic phenotypes that can be segmented into subgroups using a machine learning approach. The metabolic subgroups observed in the DO may be a useful for probing the phenotypic variability in metabolic disease observed in humans.
2022-12-30 | GSE194145 | GEO
Project description:Susceptibility to tumor development varies among mice strains. Using inbred NIH and wild-derived outbred Mus spretus backcrosses, skin cancer-susceptibility loci were mapped [Nagase et al. 1995. Nat Genet 10: 424-429; Nagase et al. 1999. Proc Natl Acad Sci USA 96: 15032-15037], and Skts13 was identified as the Aurka gene using a conventional linkage in conjunction with haplotype analysis [Ewart-Toland et al. 2003. Nat Genet 34: 403-412]. In the present study, we examined another wild-derived outbred Mus musculus castaneus in which 10.3% of the analyzed SNPs showed heterogeneity among the colony. All mice examined were completely resistant to the two-stage skin carcinogenesis protocol using 7.12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA), and this resistant phenotype was dominant when we crossed them with the highly susceptible strain FVB. By scanning F1 backcross progeny between M. m. castaneus and FVB, we found a highly significant linkage for tumor multiplicity on Chromosome 4, which was overlapped with the Skts-fp1 locus, found in the previous study using FVB and PWK cross [Fujiwara et al. 2007. BMC Genet 8: 39]. The linkage was observed in all pedigrees from the five F1 founders, while the linkage for papilloma size on Chromosome 4 was mapped only in pedigrees from founders 1 and 2. By scanning the whole Chromosome 4 of the five F1 founders, founders 1- and 2-specific haplotype block was found between D4Mit293 (20.6 Mbp) and D4Mit171 (22.4 Mbp). In this study we exploited the outbred nature of M. m. castaneus stock to identify a haplotype contributing to papilloma size on mouse Chromosome 4. These data illustrate the strength of using outbred mice in identification of the genetic component of a mouse complex trait such as the skin cancer-susceptibility phenotype.
| S-EPMC2892251 | biostudies-literature
Project description:Mycobacterium tuberculosis infects two billion people across the globe, and results in 8-9 million new tuberculosis (TB) cases and 1-1.5 million deaths each year. Most patients have no known genetic basis that predisposes them to disease. Here, we investigate the complex genetic basis of pulmonary TB by modelling human genetic diversity with the Diversity Outbred mouse population. When infected with M. tuberculosis, one-third develop early onset, rapidly progressive, necrotizing granulomas and succumb within 60 days. The remaining develop non-necrotizing granulomas and survive longer than 60 days. Genetic mapping using immune and inflammatory mediators; and clinical, microbiological, and granuloma correlates of disease identified five new loci on mouse chromosomes 1, 2, 4, 16; and three known loci on chromosomes 3 and 17. Further, multiple positively correlated traits shared loci on chromosomes 1, 16, and 17 and had similar patterns of allele effects, suggesting these loci contain critical genetic regulators of inflammatory responses to M. tuberculosis. To narrow the list of candidate genes, we used a machine learning strategy that integrated gene expression signatures from lungs of M. tuberculosis-infected Diversity Outbred mice with gene interaction networks to generate scores representing functional relationships. The scores were used to rank candidates for each mapped trait, resulting in 11 candidate genes: Ncf2, Fam20b, S100a8, S100a9, Itgb5, Fstl1, Zbtb20, Ddr1, Ier3, Vegfa, and Zfp318. Although all candidates have roles in infection, inflammation, cell migration, extracellular matrix remodeling, or intracellular signaling, and all contain single nucleotide polymorphisms (SNPs), SNPs in only four genes (S100a8, Itgb5, Fstl1, Zfp318) are predicted to have deleterious effects on protein functions. We performed methodological and candidate validations to (i) assess biological relevance of predicted allele effects by showing that Diversity Outbred mice carrying PWH/PhJ alleles at the H-2 locus on chromosome 17 QTL have shorter survival; (ii) confirm accuracy of predicted allele effects by quantifying S100A8 protein in inbred founder strains; and (iii) infection of C57BL/6 mice deficient for the S100a8 gene. Overall, this body of work demonstrates that systems genetics using Diversity Outbred mice can identify new (and known) QTLs and functionally relevant gene candidates that may be major regulators of complex host-pathogens interactions contributing to granuloma necrosis and acute inflammation in pulmonary TB.
2024-06-15 | GSE267006 | GEO
Project description:RNA-Seq of hippocampus in Diversity Outbred mice
| PRJEB31082 | ENA
Project description:RNA-Seq of Diversity Outbred mouse embryonic stem cells
| PRJEB31538 | ENA
Project description:ATAC-Seq of Diversity Outbred mouse embryonic stem cells
| PRJEB36566 | ENA