Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA152349 | 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.
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Project description:Fibrosis is defined as an abnormal matrix remodeling and loss of tissue homeostasis due to excessive synthesis and accumulation of extracellular matrix proteins in tissues. At present, there is no effective therapy for organ fibrosis. Previous studies demonstrated that aged plasminogen activator inhibitor-1(PAI-1) knockout mice develop spontaneously cardiac-selective fibrosis without affecting any other organs including kidney. Therefore, the PAI-1 knockout model of cardiac fibrosis provides an excellent opportunity to find the igniter(s) of cardiac fibrosis and its status in unaffected organs. We hypothesized that differential expressions of profibrotic and antifibrotic genes in PAI-1 knockout hearts and unaffected organs lead to cardiac selective fibrosis. In order to address this prediction, we have used a genome-wide gene expression profiling of transcripts derived from aged PAI-1 knockout hearts and kidneys. The variations of global gene expression profiling were compared within four groups: wildtype heart vs. knockout heart; wildtype kidney vs. knockout kidney; knockout heart vs. knockout kidney and wildtype heart vs. wildtype kidney. Analysis of illumina-based microarray data revealed that several genes involved in different biological processes such as immune system processing, response to stress, cytokine signaling, cell proliferation, adhesion, migration, matrix organization and transcriptional regulation were affected in hearts and kidneys by the absence of PAI-1, a potent inhibitor of urokinase- and tissue-type plasminogen activator. Importantly, the expressions of a number of genes, involved in profibrotic pathways were upregulated or downregulated in PAI-1 knockout hearts compared to wildtype hearts and PAI-1 knockout kidneys. To our knowledge, this is the first comprehensive report on the influence of PAI-1 on global gene expression profiling in the heart and kidney and its implication in several biological processes including fibrogenesis. Total RNA was extracted from hearts and kidneys derived from three PAI-1 knockout (12- month old) and three wild-type mice (12-month old) using RNeasy Fibrous Tissue Mini Kit (Qiagen, Valencia, CA) following the manufacturer’s instructions. The quality of RNA (RNA Integrity, RIN) in all 12 samples (3 wildtype hearts; 3 PAI-1 KO hearts; 3 wildtype kidneys; and 3 PAI-1 KO kidneys) was checked using the bioanalyzer. We have used a genome-wide gene expression profiling of transcripts derived from aged PAI-1 knockout hearts and kidneys. The variations of global gene expression profiling were compared within four groups: wildtype heart vs. knockout heart; wildtype kidney vs. knockout kidney; knockout heart vs. knockout kidney and wildtype heart vs. wildtype kidney.
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