Contribution of cellular retinol-binding protein type 1 to retinol metabolism during mouse development.
Within cells, retinol (ROL) is bound to cytoplasmic proteins (cellular retinol-binding proteins [CRBPs]), whose proposed function is to protect it from unspecific enzymes through channeling to retinoid-metabolizing pathways. We show that, during development, ROL and retinyl ester levels are decreased in CRBP type 1 (CRBP1) -deficient embryos and fetuses by 50% and 80%, respectively. The steady state level of retinoic acid (RA) is also decreased but to a lesser extent. However, CRBP1-null fetuses do not exhibit the abnormalities characteristic of a vitamin A-deficiency syndrome. Neither CRBP1 deficiency alters the expression patterns of RA-responding genes during development, nor does CRBP1 availability modify the expression of an RA-dependent gene in primary embryonic fibroblasts treated with ROL. Therefore, CRBP1 is required in prenatal life to maintain normal amounts of ROL and to ensure its efficient storage but seems of secondary importance for RA synthesis, at least under conditions of maternal vitamin A sufficiency.
Matt
Nicolas
N
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut Clinique de la Souris (ICS), CNRS/INSERM/ULP, Collège de France, BP10142, 67404 Illkirch Cedex, CU de Strasbourg, France.
Schmidt
Carsten K
CK
Dupé
Valérie
V
Dennefeld
Christine
C
Nau
Heinz
H
Chambon
Pierre
P
Mark
Manuel
M
Ghyselinck
Norbert B
NB
D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D017930:Genes, Reporter; D006706:Homeostasis / Q000502:physiology; D051379:Mice; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054840:Retinol-Binding Proteins, Cellular; D014212:Tretinoin / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism*
D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D014801:Vitamin A; D014212:Tretinoin