Project description:Microarray analysis of liver tissue from WT SIRT6 and conditional knockout of SIRT6 using albumin-Cre (SIRT6Co/Co ;Alb-Cre) at 2 and 8 months of age
Project description:Microarray analysis of liver tissue from WT SIRT6 and conditional knockout of SIRT6 using albumin-Cre (SIRT6Co/Co ;Alb-Cre) at 2 and 8 months of age RNA was extracted from mouse liver tissue at 2 and 8 months of age. RNA from three pairs of WT SIRT6 and SIRT6Co/Co ;Alb-Cre mice was combined and hybridized to Affymetrix mouse gene 1.0 ST arrays.
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: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:Fenofibrate is a specific agonist of the nuclear receptor PPARa. To identify the gene expression under the strict dependence of hepatic PPARa activity, we generated a new mouse strain of PPARa-specific deletion in hepatocyte (albumin-Cre+/- Pparaflox/flox or LKO) and we compared them to total Ppara KO (KO), wild-type (WT) and liver WT (albumin-Cre-/- Pparaflox/flox or LWT) mice. We used microarrays to detail the global programme of gene expression in liver of Ppara LKO, LWT, Ppara KO and WT male mice.
Project description:As a member of class III histone deacetylases, Sirt6 has various functions including regulation of genomic stability, DNA repair, cancer, metabolism and ageing.Deficiency of Sirt6 is lethal and causes brain development redardation. We generated Emx1-cre induced Sirt6 conditional knockout mice model and found that Sirt6 deficiency promoted self-renew of neural precursor cells (NPCs) and inhibited differentiation. This result promotes understanding of the role of Sirt6 in brain development and NPCs’ fate determination and provides clues to explain the generality and difference between species.
