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 be mediated in part by the three nuclear receptors (RAR alpha, -beta, and -gamma), each of which is expressed as multiple isoforms. To investigate the function of the RAR alpha gene, we have disrupted, in the mouse, the whole gene or the isoform RAR alpha 1. Although RAR alpha 1 is the predominant isoform and is highly conserved among vertebrates, RAR alpha 1-null mice appeared normal. However, targeted disruption of the whole RAR alpha gene resulted in early postnatal lethality and testis degeneration. These results, showing that RAR alpha is indeed involved in the transduction of the RA signal, also suggest an unexpected genetic redundancy.