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 and fertile. They do not present any of the congenital abnormalities related to retinoic acid (RA) deficiency, indicating that CRBPI is not indispensable for RA synthesis. However, CRBPI deficiency results in an approximately 50% reduction of retinyl ester (RE) accumulation in hepatic stellate cells. This reduction is due to a decreased synthesis and a 6-fold faster turnover, which are not related to changes in the levels of RE metabolizing enzymes, but probably reflect an impaired delivery of ROL to lecithin:retinol acyltransferase. CRBPI-null mice fed a vitA-deficient diet for 5 months fully exhaust their RE stores. Thus, CRBPI is indispensable for efficient RE synthesis and storage, and its absence results in a waste of ROL that is asymptomatic in vitA-sufficient animals, but leads to a severe syndrome of vitA deficiency in animals fed a vitA-deficient diet.
Ghyselinck
N B
NB
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Collège de France, 67404 Illkirch Cedex.
Båvik
C
C
Sapin
V
V
Mark
M
M
Bonnier
D
D
Hindelang
C
C
Dierich
A
A
Nilsson
C B
CB
Håkansson
H
H
Sauvant
P
P
Azaïs-Braesco
V
V
Frasson
M
M
Picaud
S
S
Chambon
P
P
D000818:Animals; D005260:Female; D006706:Homeostasis; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012177:Retinol-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D054840:Retinol-Binding Proteins, Cellular; D014801:Vitamin A / Q000008:administration & dosage / Q000378:metabolism*; D014802:Vitamin A Deficiency / Q000378:metabolism / Q000473:pathology
D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D014801:Vitamin A