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Cellular retinol‐binding protein I is essential for vitamin A homeostasis
Author(s) -
Ghyselinck Norbert B.,
Båvik Claes,
Sapin Vincent,
Mark Manuel,
Bonnier Dominique,
Hindelang Colette,
Dierich Andrée,
Nilsson Charlotte B.,
Håkansson Helen,
Sauvant Patrick,
AzaïsBraesco Véronique,
Frasson Maria,
Picaud Serge,
Chambon Pierre
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.18.4903
Subject(s) - biology , retinol , vitamin a deficiency , endocrinology , retinol binding protein , medicine , retinoic acid , acyltransferase , vitamin , homeostasis , mutant , enzyme , biochemistry , gene
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 ∼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.