Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein

Retinol-binding protein (RBP) is the sole specific transport protein for re tinol (vitamin A) in the circulation, and its single known function is to d eliver retinol to tissues. Within tissues, retinol is activated to retinoic acid, which binds to nuclear receptors to regulate transcription of >300 d iverse target genes. In the eye, retinol is also activated to 11-cis-retina l, the visual chromophore, We generated REP knockout mice (RBP-/-) by gene targeting. These mice have several phenotypes. Although viable and fertile, they have reduced blood retinol levels and markedly impaired retinal funct ion during the first months of life. The impairment is not due to developme ntal retinal defect. Given a vitamin A-sufficient diet, the RBP-/- mice acq uire normal vision by 5 months of age even though blood retinol levels rema in low, Deprived of dietary vitamin A, vision remains abnormal and blood re tinol declines to undetectable levels. Another striking phenotype of the mu tant mice is their abnormal retinol metabolism. The RBP-/- mice can acquire hepatic retinol stores, but these cannot be mobilized. Thus, their vitamin A status is extremely tenuous and dependent on a regular vitamin A intake, Unlike wild-type mice, serum retinol levels in adult RBP-/- animals become undetectable after only a week on a vitamin A-deficient diet and their ret inal function rapidly deteriorates, Thus REP is needed for normal vision in young animals and for retinol mobilization in times of insufficient dietar y intake, but is otherwise dispensable for the delivery of retinol to tissu es.