Submitted to: Plant and Animal Genome Conference
Publication Type: Abstract Only
Publication Acceptance Date: 12/14/2006
Publication Date: N/A
Citation: Interpretive Summary:
Technical Abstract: Previously, we have generated myostatin propeptide transgenic mice. Expression of the propeptide transgene at 5% of beta-actin mRNA level results in 17-30% increase in growth rate, and 22-44% increase in carcass weight at 9 weeks of age. The total mass of the main muscles of transgenic mice increased by 98.8–132.9% compared to non-transgenic mice at 6 months of age. Analysis of muscle histochemistry indicates that the cross-sectional areas of fast-twitch glycolytic fibers are 60% larger in transgenic mice than that in non-transgenic mice while fiber number was not different. The muscular phenotype of the transgenic mice results from muscle fiber hypertrophy rather than hyperplasia. To investigate gene expression patterns of hypertrophic muscle fiber, we did a comparison of microarray analysis between transgenic mice and non-transgenic littermate mice. A mouse array, GeneChip Mouse Genome 430 2.0 Array (Affymetrix), was used for this study. Of 45,000 probe sets, this array contains over 34,000 well-characterized genes. Following the statistical model described by Affymetrix GCOS software, we identified more than 200 genes or expressed sequence tags differentially expressed by hypertrophic muscle of the transgenic mice at the statistical significance of P<0.0001. A preliminary cluster analysis of these genes indicates several categories of gene functions are up-regulated in muscle fiber hypertrophy, including myogenesis, TGF-related signaling proteins, muscle structure proteins, proteinase inhibitors, glucose transporters and carrier proteins. However, the genes related to mitochondrion metabolism and RNA synthesis are down-regulated. The results support several coordinated patterns of gene expressions in controlling muscle fiber hypertrophy in the myostatin prodomain transgenic mice.