PARTIAL HORMONE RESISTANCE IN MICE WITH DISRUPTION OF THE STEROID-RECEPTOR COACTIVATOR-1 (SRC-1) GENE

The in vivo biological function of a steroid receptor coactivator was assessed in mice in which the SRC-1 gene was inactivated by gene targe ting. Although in both sexes the homozygous mutants were viable and fe rtile, target organs such as uterus, prostate, testis, and mammary gla nd exhibited decreased growth and development in response to steroid h ormones. Expression of RNA encoding TIF2, a member of the SRC-1 family , was increased in the SRC-1 null mutant, perhaps compensating partial ly for the loss of SRC-1 function in target tissues, The results indic ate that SRC-1 mediates steroid hormone responses in vivo and that los s of its coactivator function results in partial resistance to hormone .