GENE-EXPRESSION OF RETINOIC ACID RECEPTORS AND CELLULAR RETINOIC ACID-BINDING PROTEINS IN RHINO AND HAIRLESS MOUSE SKIN

The rhino mouse comedolytic model and the hairless mouse photoaging model are established animal models for screening the in vivo activity of retinoids. However, the expression of the retinoic acid receptors (RARs) and cellular retinoic acid-binding proteins (CRABPs), known to regulate retinoid activity, is not completely understood in these mouse mutants. For this purpose, mRNA was isolated from rhino and hairless mouse skin and the gene expression of the RARs and CRABPs was measured by Northern blot hybridization. Results showed that RAR gamma was the predominantly expressed RAR in both mouse strains. Two isoforms of RAR gamma, RAR gamma 1 and RAR gamma 2, were detected with RAR gamma 1 being the more strongly expressed. RAR alpha was also detected, but to a lesser degree than RAR gamma. RAR beta expression was not detectable by our methodology. Additionally, topical treatment of these mice with 0.1% all-trans-retinoic acid (tRA) cream resulted in no significant alteration in the expression of the RAR genes. By contrast, CRABP-II was induced 2-4 fold by topical tRA treatment, CRABP-I, expressed to a lesser degree than CRABP-II, was not inducible, The relative expression of the RARs, CRABPs, and inducibility of CRABP-II by tRA in both rhino and hairless mouse skin paralleled that reported for human and mouse skin. These observations suggest that the altered phenotype observed in the rhino mouse most likely does not result from an altered expression level of these genes. The results also support these two animals as models for evaluating the therapeutic potential of retinoids.