Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein.
Retinol-binding protein (RBP) is the sole specific transport protein for retinol (vitamin A) in the circulation, and its single known function is to deliver retinol to tissues. Within tissues, retinol is activated to retinoic acid, which binds to nuclear receptors to regulate transcription of >300 diverse target genes. In the eye, retinol is also activated to 11-cis-retinal, the visual chromophore. We generated RBP 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 function during the first months of life. The impairment is not due to developmental retinal defect. Given a vitamin A-sufficient diet, the RBP(-/-) mice acquire normal vision by 5 months of age even though blood retinol levels remain low. Deprived of dietary vitamin A, vision remains abnormal and blood retinol declines to undetectable levels. Another striking phenotype of the mutant 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 retinal function rapidly deteriorates. Thus RBP is needed for normal vision in young animals and for retinol mobilization in times of insufficient dietary intake, but is otherwise dispensable for the delivery of retinol to tissues.
Quadro
L
L
Institute of Cancer Research, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Blaner
W S
WS
Salchow
D J
DJ
Vogel
S
S
Piantedosi
R
R
Gouras
P
P
Freeman
S
S
Cosma
M P
MP
Colantuoni
V
V
Gottesman
M E
ME
D000367:Age Factors; D000818:Animals; D001682:Biological Availability; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D004596:Electroretinography; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008957:Models, Genetic; D012160:Retina / Q000502:physiology; D012177:Retinol-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors; D019076:Transgenes; D014785:Vision, Ocular / Q000502:physiology; D014801:Vitamin A / Q000097:blood / Q000378:metabolism*
D012177:Retinol-Binding Proteins; D014801:Vitamin A