Project description:Several studies have shown that bone mineral density (BMD), a clinically measurable predictor of osteoporotic fracture, is the sum of genetic and environmental influences. In addition, serum IGF-1 levels have been correlated to both BMD and fracture risk. We previously identified a Quantitative Trait Locus (QTL) for Bone Mineral Density (BMD) on mouse Chromosome (Chr) 6 that overlaps a QTL for serum IGF-1. The B6.C3H-6T (6T) congenic mouse is homozygous for C57BL/6J (B6) alleles across the genome except for a 30 cM region on Chr 6 that is homozygous for C3H/HeJ (C3H) alleles. This mouse was created to study biology behind both the BMD and the serum IGF-1 QTLs and to identify the gene(s) underlying these QTLs. Female 6T mice have lower BMD and lower serum IGF-1 levels at all ages measured. As the liver is the major source of serum IGF-1, we examined differential expression in the livers of fasted female B6 and 6T mice by microarray. Keywords: Genetic variation
Project description:Sex differences in liver gene expression are dictated by sex-differences in circulating growth hormone (GH) profiles. Presently, the pituitary hormone dependence of mouse liver gene expression was investigated on a global scale to discover sex-specific early GH response genes that might contribute to sex-specific regulation of downstream GH targets and to ascertain whether intrinsic sex-differences characterize hepatic responses to plasma GH stimulation. RNA expression analysis using 41,000-feature microarrays revealed two distinct classes of sex-specific mouse liver genes: genes subject to positive regulation (class-I) and genes subject to negative regulation by pituitary hormones (class-II). Genes activated or repressed in hypophysectomized (Hypox) mouse liver within 30-90min of GH pulse treatment at a physiological dose were identified as direct targets of GH action (early response genes). Intrinsic sex-differences in the GH responsiveness of a subset of these early response genes were observed. Notably, 45 male-specific genes, including five encoding transcriptional regulators that may mediate downstream sex-specific transcriptional responses, were rapidly induced by GH (within 30min) in Hypox male but not Hypox female mouse liver. The early GH response genes were enriched in 29 male-specific targets of the transcription factor Mef2, whose activation in hepatic stellate cells is associated with liver fibrosis leading to hepatocellular carcinoma, a male-predominant disease. Thus, the rapid activation by GH pulses of certain sex-specific genes is modulated by intrinsic sex-specific factors, which may be associated with prior hormone exposure (epigenetic mechanisms) or genetic factors that are pituitary-independent, and could contribute to sex-differences in predisposition to liver cancer or other hepatic pathophysiologies.
Project description:Several studies have shown that bone mineral density (BMD), a clinically measurable predictor of osteoporotic fracture, is the sum of genetic and environmental influences. In addition, serum IGF-1 levels have been correlated to both BMD and fracture risk. We previously identified a Quantitative Trait Locus (QTL) for Bone Mineral Density (BMD) on mouse Chromosome (Chr) 6 that overlaps a QTL for serum IGF-1. The B6.C3H-6T (6T) congenic mouse is homozygous for C57BL/6J (B6) alleles across the genome except for a 30 cM region on Chr 6 that is homozygous for C3H/HeJ (C3H) alleles. This mouse was created to study biology behind both the BMD and the serum IGF-1 QTLs and to identify the gene(s) underlying these QTLs. Female 6T mice have lower BMD and lower serum IGF-1 levels at all ages measured. As the liver is the major source of serum IGF-1, we examined differential expression in the livers of fasted female B6 and 6T mice by microarray. Experiment Overall Design: The experimental design of this experiment was a simple two-factor experiment, with three biological replicates of each factor (in this case mouse strain, B6.C3H-6T vs. C57BL/6J).
Project description:To investigate the differences in microRNA expression profiles between fibrotic and normal livers, we performed microRNA microarrays for total RNA extracts isolated from mouse livers treated with carbontetrachloride (CCl4) or corn-oil for 10 weeks (n=3/group). MicroRNAs were considered to have significant differences in expression level when the expression difference showed more than two-fold change between the experimental and control groups at p<0.05. We found that 12 miRNAs were differentially expressed in CCl4-induced fibrotic liver.
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:A transcriptome study in mouse hematopoietic stem cells was performed using a sensitive SAGE method, in an attempt to detect medium and low abundant transcripts expressed in these cells. Among a total of 31,380 unique transcript, 17,326 (55%) known genes were detected, 14,054 (45%) low-copy transcripts that have no matches to currently known genes. 3,899 (23%) were alternatively spliced transcripts of the known genes and 3,754 (22%) represent anti-sense transcripts from known genes.