HIGH POSTNATAL LETHALITY AND TESTIS DEGENERATION IN RETINOIC ACID RECEPTOR-ALPHA MUTANT MICE

Retinoic acid (RA) plays a critical role in normal development, growth , and maintenance of certain tissues. The action of RA is thought to b e mediated in part by the three nuclear receptors (RARalpha, -beta, an d -gamma), each of which is expressed as multiple isoforms. To investi gate the function of the RARalpha gene, we have disrupted, in the mous e, the whole gene or the isoform RARalpha1. Although RARalpha1 is the predominant isoform and is highly conserved among vertebrates, RARalph a1-null mice appeared normal. However, targeted disruption of the whol e RARalpha gene resulted in early postnatal lethality and testis degen eration. These results, showing that RARalpha is indeed involved in th e transduction of the RA signal, also suggest an unexpected genetic re dundancy.