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 better understand the temporal dynamics of gene expression during normal murine lung development we characterized global gene expression at 26 time points in three common inbred strains of mice (A/J, C57BL/6J, and C3H/HeJ). The data set provides a unique resource for identifying patterns of gene expression changes during normal lung development and for investigating the developmental origins of respiratory disease. The transcriptional profiles generated for lung development in three inbred strains of the laboratory mouse revealed concordance with pre-natal stages of lung development defined by anatomy and morphology. The genomic data support the view that the postnatal alveolar development is composed of 4 distinct molecular stages. The data revealed strain specific differences in the expression of genes related to respiratory cell differentiation, pulmonary innervation, metabolic pathway interactions, and immune system function.
Project description:PURPOSE: To provide a detailed gene expression profile of the normal postnatal mouse cornea. METHODS: Serial analysis of gene expression (SAGE) was performed on postnatal day (PN)9 and adult mouse (6 week) total corneas. The expression of selected genes was analyzed by in situ hybridization. RESULTS: A total of 64,272 PN9 and 62,206 adult tags were sequenced. Mouse corneal transcriptomes are composed of at least 19,544 and 18,509 unique mRNAs, respectively. One third of the unique tags were expressed at both stages, whereas a third was identified exclusively in PN9 or adult corneas. Three hundred thirty-four PN9 and 339 adult tags were enriched more than fivefold over other published nonocular libraries. Abundant transcripts were associated with metabolic functions, redox activities, and barrier integrity. Three members of the Ly-6/uPAR family whose functions are unknown in the cornea constitute more than 1% of the total mRNA. Aquaporin 5, epithelial membrane protein and glutathione-S-transferase (GST) omega-1, and GST alpha-4 mRNAs were preferentially expressed in distinct corneal epithelial layers, providing new markers for stratification. More than 200 tags were differentially expressed, of which 25 mediate transcription. CONCLUSIONS: In addition to providing a detailed profile of expressed genes in the PN9 and mature mouse cornea, the present SAGE data demonstrate dynamic changes in gene expression after eye opening and provide new probes for exploring corneal epithelial cell stratification, development, and function and for exploring the intricate relationship between programmed and environmentally induced gene expression in the cornea. Keywords: other
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 M-bM-^@M-^Xhotspots,M-bM-^@M-^Y 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 M-bM-^@M-^XfertileM-bM-^@M-^Y 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. Gene expression was measured in whole testis in males aged 70(M-BM-15) days. Samples include 294 WSB/EiJ x PWD/PhJ F2s, 11 PWD/PhJ x WSB/EiJ F2s, 8 WSB/EiJ, 8 PWD/PhJ, 6 PWD/PhJ x WSB/EiJ F1s and 4 WSB/EiJ x PWD/PhJ F1s.
Project description:To better understand the temporal dynamics of gene expression during normal murine lung development we characterized global gene expression at 26 time points in three common inbred strains of mice (A/J, C57BL/6J, and C3H/HeJ). The data set provides a unique resource for identifying patterns of gene expression changes during normal lung development and for investigating the developmental origins of respiratory disease. The transcriptional profiles generated for lung development in three inbred strains of the laboratory mouse revealed concordance with pre-natal stages of lung development defined by anatomy and morphology. The genomic data support the view that the postnatal alveolar development is composed of 4 distinct molecular stages. The data revealed strain specific differences in the expression of genes related to respiratory cell differentiation, pulmonary innervation, metabolic pathway interactions, and immune system function. Mouse lungs or whole embryos (e09.5 only) were surgically dissected at 26 time points across all six canonical stages of lung development (embryonic-EMB, pseudoglandular-PSG, canalicular-CAN, saccular-SAC, alveolar-ALV, homeostatic-HOM) to identify transcriptional profiles associated with 9 molecular divisions of lung development (embryonic-EMB, pseudoglandular-PSG, canalicular-CAN, saccular-SAC, alveolar1-ALV1, alveolar2-ALV2, alveolar3-ALV3, alveolar4-ALV4, homeostatic-HOM). Lung tissue from three or four embryos collected at e11.5 or e12.5, respectively, was pooled for each sample to obtain sufficient RNA for array analysis. Tissue from at least three animals was collected for each time point (biological replicates). Only male mice were used in the study.
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from Mus musculus tissues (Heart, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from seven Mus musculus tissues (Heart, Brain, Liver, Lung, Kidney, Skeletal Muscle, Thymus)