Effects of Growth Hormone Resistance on Gene Expression: Studies in GHR-KO (Laron Dwarf) mice





K Cochran, M J Iqbal, B Bailey, and A Bartke

Southern Illinois University Carbondale, 791 Crowell Rd Apt 1, Carbondale, IL 62901



The GHR-KO (Laron Dwarf) mouse is a novel animal model for aging studies. GHR-KO animals are growth hormone resistant, IGF-I deficient, and live longer than their normal (wild type, WT) siblings. Maximal life span (defined as average longevity of the longest living 15% of each sex/genotype group) was significantly increased in both male and female GHR-KO as compared to normal mice. It is known or suspected that development of age-related pathology including cancer is prevented or delayed in these animals. This study was undertaken to screen for possible changes in the expression of genes involved in the regulation of cell cycle and apoptosis in young adult GHR-KO mice. Normal and GHR-KO mice were sacrificed at 2 months of age. Internal organs such as spleen (n=6), liver (n=14), kidney (n=6) and brain (n=6) were collected. In each case samples from two mice were pooled for analysis via Superarray Inc. Pathway Finder expression arrays. These macro arrays carried genes that were specific for signal transduction pathways involved in cancer, apoptosis, and cell cycle regulation. Analysis of the data after normalization and correction revealed tissue specific differences in gene expression between WT and GHR-KO mice. In the liver there was significant increase in the expression of gadd45 and ikBa (p<.05) a suggestive increase in IL-2 (p<.1). There were suggestive decreases in the expression of p16ink4a in the kidney, and gadd45 and hsp86 in the brain (p<.1). Verification of these results by other procedures and further studies in middle-aged and aging animals should allow us to formulate hypotheses concerning mechanisms of delayed aging in GHR-KO mice. Supported by NIH (AG19899) and Illinois CFAR.




Key words: Growth Hormone Expression Array







Problems or questions regarding this site should be directed to webmaster@americanaging.org