Cellular retinol-binding protein I is essential for vitamin A homeostasis

The gene encoding cellular retinol (ROL, vitA)-binding protein type I(CRBPI ) has been inactivated. Mutant mice fed a vitA-enriched diet are healthy an d fertile. They do not present any of the congenital abnormalities related to retinoic acid (RA) deficiency, indicating that CRBPI is not indispensabl e for RA synthesis, However, CRBPI deficiency results in an similar to 50% reduction of retinyl ester (RE) accumulation in hepatic stellate cells. Thi s reduction is due to a decreased synthesis and a 6-fold faster turnover, w hich are not related to changes in the levels of RE metabolizing enzymes, b ut probably reflect an impaired delivery of ROL to lecithin:retinol acyltra nsferase. CRBPI-null mice fed a vitA-deficient diet for 5 months fully exha ust their RE stores. Thus, CRBPI is indispensable for efficient RE synthesi s and storage, and its absence results in a waste of ROL that is asymptomat ic in vitA-sufficient animals, but leads to a severe syndrome of vitA defic iency in animals fed a vitA-deficient diet.