MICE DEFICIENT IN CELLULAR RETINOIC ACID-BINDING PROTEIN-II (CRABPII)OR IN BOTH CRABPI AND CRABPII ARE ESSENTIALLY NORMAL

We have disrupted the CRABPII gene using homologous recombination in e mbryonic stem cells, and shown that this disruption results in a null mutation. CRABPII null mutant mice are essentially indistinguishable f rom wild-type mice as judged by their normal development, fertility, l ife span and general behaviour, with the exception of a minor limb mal formation. Moreover, CRABPI(-/-)/CRABPII(-/-) double mutant mice also appear to be essentially normal, and both CRABPII(-/-) single mutant a nd CRABPI(-/-)/CRABPII(-/-) mutant embryos are not more sensitive than wildtype embryos to retinoic acid excess treatment in utero. Thus, CR ABPI and CRABPII are dispensable both during mouse development and adu lt life. Our present results demonstrate that CRABPs are not criticall y involved in the retinoic acid signaling pathway, and that none of th e functions previously proposed for CRABPs are important enough to acc ount for their evolutionary conservation.