REGULATION OF THE MOUSE CELLULAR RETINOIC ACID-BINDING PROTEIN-I GENEBY THYROID-HORMONE AND RETINOIDS IN TRANSGENIC MOUSE EMBRYOS AND P19 CELLS

The regulation of mouse cellular retinoic acid-binding protein-I (CRAB P-I) gene expression by the retinoids and thyroid hormones was examine d, by using a beta-galactosidase (lacZ) reporter gene and a CRABP-I sp ecific antibody, in transgenic mouse embryos and a mouse embryonal car cinoma cell line P19. The CRABP-lacZ reporter gene expression recapitu lated the expression pattern of endogenous CRABP-I in the developing c entral nervous system. In mid-gestation mouse embryos the expression o f both the transgene and the endogenous protein was elevated under the condition of hypovitaminosis A, suggesting that depletion of retinoic acid (RA) induced CRABP-I expression in embryos. Consistently, this r eporter was suppressed by RA in P19 cells. In co-transfection experime nts it was demonstrated that the expression of RAR beta, RAR gamma or RXR alpha suppressed this reporter expression. In experiments designed to alter the thyroid hormone status in animals it was demonstrated th at both the reporter gene and the endogenous CRABP-I expression were r educed by triiodothyronine injection and were elevated in a hypothyroi dic condition induced by feeding with iodine-deficient diet supplement ed with 6-propyl-2-thiouracil. In co-transfection experiments it was a lso demonstrated that the expression of T3R beta suppressed the report er expression in P19 cells. It was concluded that RA had a suppressive effect on CRABP-I gene expression in embryos and P19 cells and the ef fect could be mediated through RAR beta, RAR gamma or RXR alpha. A rol e of thyroid hormones in CRABP-I gene expression and vitamin A metabol ism in animals is discussed.