ROLE OF THE RETINOIC ACID RECEPTOR-BETA (RAR-BETA) DURING MOUSE DEVELOPMENT

Homozygous RAR beta mutants are growth-deficient, but are fertile and have a normal longevity. They display homeotic transformations and mal formations of cervical vertebrae and a retrolenticular membrane. This latter abnormality arises from the persistence and hyperplasia of the primary vitreous body. In contrast, we found that abnormalities of cra nial nerves IX and X which were previously proposed to be specific fea tures of the RAR beta mutant phenotype (Luo at al., Mech. Dev. 53: 61- 71, 1995) occur with the same low penetrance in wildtype littermates. Although the RAR beta protein is expressed at high levels in the stria tum and interdigital mesenchyme, the brain and limbs of RAR beta mutan ts appear morphologically normal. RAR alpha/RAR beta double mutants di splay numerous visceral abnormalities, most of which are incompatible with post-natal life. The majority of these abnormalities was previous ly detected in RAR alpha/RAR beta 2 mutants with the notable exception s of agenesis of the stapedial (2nd aortic arch-derived) artery, thymi c and spleen agenesis and abnormal inferior vena cava. RAR beta/RAR ga mma double mutants show major ocular defects including a shortening of the ventral retina and pre-natal retinal dysplasia, both of which rep resent the only abnormalities of the fetal vitamin-A deficiency (VAD) syndrome not previously detected in RAR beta 2/RAR gamma compound muta nts. In addition, RAR beta is apparently functionally redundant with e ither RAR alpha or RAR gamma for the formation of a small subset of cr aniofacial skeletal elements, as well as for eyelid development and di git separation. We also provide evidence that, at least in some instan ces, this phenomenon of functional redundancy between RARs may be an a rtifactual consequence of gene knock-out.