Gene Expression Profile of Long-Lived Snell Dwarf Mice

Abstract

To gain further insight into the basis for the extended longevity and delayed aging of Snell dwarf (dw/dw) mice, we have measured levels of expression of 2352 genes in liver of mice at 6 months of age. We find 60 genes for the which the Student's t statistic meets the arbitrary criterion of p <.001, and among these 17 meet the Bonferroni-adjusted significance criterion at p <.05, which corresponds to a nominal value of p <.00002. Using the Bonferroni criterion, we find that dwarf mice show increases in liver mRNA for two mannose-binding lectins, two DNA binding proteins, serum amyloid P component, corticosteroid-binding globulin, and insulin-like growth factor-binding protein 2, as well as decreases in a two phosphodiesterases, a pheromone-binding urinary protein, insulin-like growth factor-I (IGF-I), a calcium-binding protein calgranulin B, a deubiquitinating enzyme, a hydroxysteroid dehydrogenase, a DNA methyltransferase, a glycine transporter, and a placental lactogen. We also use this data set to compare the results of different suggested criteria for evaluating intergroup differences in gene expression. Of the 2352 genes examined, 524 (22%) showed a twofold difference between dwarf and normal mice, but most of these fail to meet the conventional significance criterion of p <.05, let alone criteria that have been adjusted to compensate for multiple comparison artifacts. The list of genes that show reliable differences between dwarf and control animals provides new insights into the range of changes induced by deficiencies in growth hormone, thyroid-stimulating hormone, and prolactin, and it will help to guide further studies of the pathways by which these hormone deficiencies contribute to delayed aging in these mutant mice.