Project description:We created mice, which are deficient for Myc specifically in cardiac myocytes by crossing crossed Myc-floxed mice (Mycfl/fl) and MLC-2VCre/+ mice. Serial analysis of earlier stages of gestation revealed that Myc-deficient mice died prematurely at E13.5-14.5. Morphological analyses of E13.5 Myc-null embryos showed normal ventricular size and structure; however, decreased cardiac myocyte proliferation and increased apoptosis was observed. BrdU incorporation rates were also decreased significantly in Myc-null myocardium. Myc-null mice displayed a 3.67-fold increase in apoptotic cardiomyocytes by TUNEL assay. We examined global gene expression using oligonucleotide microarrays. Numerous genes involved in mitochondrial death pathways were dysregulated including Bnip3L and Birc2. Keywords: wildtype vs Myc-null
Project description:Description: Progranulin deficiency is associated with neurodegeneration in humans and in mice. We performed a deep proteomic screen of the pre-frontal cortex in aged (13-15 months) female progranulin-deficient mice (GRN-/-) and mice with a neuron-specific inducible overexpression of progranulin (SLICK-GRN-OE with tamoxifen) versus the respective control mice (Grn+/+ and SLICK-Grn without Tamoxifen). The data set shows progranulin-dependent alterations of protein expression in the cortex of mice.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
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.
Project description:Transcriptomic profiling of mouse brain in old progranulin deficient mice with a complete loss of progranulin (PGRN KO), with restoration of neuronal progranulin (NesGrnOE-KOBG), in progranulin-EGFL7 double deficient mice (EGFL7-PGRNdko) and floxed control mice (Grnflfl) Genetic progranulin deficiency in humans causes Frontotemporal Dementia (FTD). Progranulin knockout mice (PGRNko) are a model for the disease albeit cognitive impairment in mice is subtle. The predominant FTD-phenotype in mice are hyperactivity, sugar craving, compulsiveness, skin lesions owing to exessive grooming and general health issues in old mice such as anal prolaps. Progranulin in primarily expressed in neurons and in myeloid derived immune cells including microglia. Progranulin deficient microglia are neuron-aggressive and are believed to contribute to excessive synaptic pruning. It is not known if progranulin that is normally neurotrophic and keeps microglia in a neuron-supportive phenotype has to come from within microglia or is a progranulin-signal from neurons to microglia. To dissect out the differential contribution we generated mice which express progranulin in neurons via Nestin-driven restoration of progranulin expression in a progranulin knockout background. In addition we assessed additional deletion of EGFL7, which behaves as progranulin competitor for binding/activation of NOTCH receptors. Hence, this study describes and compared the transcriptome of old mice in four mouse lines: full progranulin knockout (PGRNko), neuronal resoration of PGRN on a knockout background (NesGrnOE-koBG), progranulin & EGFL7 double deletion (EGFL7-PGRNdko) and floxed progranulin control mice (Grn flfl). Mice were 60-70 weeks old at the the time of tissue collection. Total RNA was extracted with Qiagen RNAeasy micro-kits and sequencing librariers were prepared by Novogene according to standard protocols for mRNA sequencing. RNA seq was done on Illumina NovaSeq 6000. The sequence alignment was done with standard proceduers including quality filtering and adapter trimming with Qiagen's CLC Genomic Workbench. The TMM (trimmed mean od M-values) algorithm was used for read normalization. Total reads, RPKM and TPM are also provided in "Processed data" files.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility. Gene expression was measured in whole testis from males aged 62-86 days. Samples include 190 first generation lab-bred male offspring of wild-caught mice from the Mus musculus musculus - M. m. domesticus hybrid zone.
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility.
Project description:To study effect of VRK1 deletion on spermatogenesis of the mouse, transciptomic analysis of genes in postnatal 8-day testicular cells of wild type and VRK1-deficient Mus musculus was performed. Gene expression in testes from from wild type and VRK1-deficient mutant Mus musculus, respectively, was measured. Four independent experiments for wild type and mutant, respectively, were performed.
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.
Project description:We created mice, which are deficient for Myc specifically in cardiac myocytes by crossing crossed Myc-floxed mice (Mycfl/fl) and MLC-2VCre/+ mice. Serial analysis of earlier stages of gestation revealed that Myc-deficient mice died prematurely at E13.5-14.5. Morphological analyses of E13.5 Myc-null embryos showed normal ventricular size and structure; however, decreased cardiac myocyte proliferation and increased apoptosis was observed. BrdU incorporation rates were also decreased significantly in Myc-null myocardium. Myc-null mice displayed a 3.67-fold increase in apoptotic cardiomyocytes by TUNEL assay. We examined global gene expression using oligonucleotide microarrays. Numerous genes involved in mitochondrial death pathways were dysregulated including Bnip3L and Birc2. Hearts were taken from wide type and Myc-null Mouse embryos at E13.5 under the dissecting scope. Cardiac myocyte RNA was isolated using TRIZOL®Reagent Total RNA (100 ng) was hybridized to the Sentrix® MouseRef-8 Expression BeadChip that contains probes for ~24,000 transcripts. GeneChips were scanned using the Hewlett-Packard GeneArray Scanner G2500A. The data were analyzed with Illumina Inc. BeadStudio version 1.5.0.34 and normalized by rank invariant method.