Disruption of the lecithin:retinol acyltransferase gene makes mice more susceptible to vitamin A deficiency.
Lecithin:retinol acyltransferase (LRAT) catalyzes the esterification of retinol (vitamin A) in the liver and in some extrahepatic tissues, including the lung. We produced an LRAT gene knock-out mouse strain and assessed whether LRAT-/- mice were more susceptible to vitamin A deficiency than wild type (WT) mice. After maintenance on a vitamin A-deficient diet for 6 weeks, the serum retinol level was 1.34 +/- 0.32 microM in WT mice versus 0.13 +/- 0.06 microM in LRAT-/- mice (p < 0.05). In liver, lung, eye, kidney, brain, tongue, adipose tissue, skeletal muscle, and pancreas, the retinol levels ranged from 0.05 pmol/mg (muscle and tongue) to 17.35 +/- 2.66 pmol/mg (liver) in WT mice. In contrast, retinol was not detectable (<0.007 pmol/mg) in most tissues from LRAT-/- mice after maintenance on a vitamin A-deficient diet for 6 weeks. Cyp26A1 mRNA was not detected in hepatic tissue samples from LRAT-/- mice but was detected in WT mice fed the vitamin A-deficient diet. These data indicate that LRAT-/- mice are much more susceptible to vitamin A deficiency and should be an excellent animal model of vitamin A deficiency. In addition, the retinol levels in serum rapidly increased in the LRAT-/- mice upon re-addition of vitamin A to the diet, indicating that serum retinol levels in LRAT-/- mice can be conveniently modulated by the quantitative manipulation of dietary retinol.
Liu
Limin
L
Department of Pharmacology, Weill Medical College of Cornell University, New York, New York 10021, USA.
Gudas
Lorraine J
LJ
D000217:Acyltransferases / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005091:Exons; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D005838:Genotype; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D009154:Mutation; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000072516:Retinoic Acid 4-Hydroxylase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014018:Tissue Distribution; D014212:Tretinoin / Q000378:metabolism; D014801:Vitamin A / Q000097:blood / Q000378:metabolism; D014802:Vitamin A Deficiency / Q000235:genetics*
D012333:RNA, Messenger; D014801:Vitamin A; D014212:Tretinoin; D012313:RNA; D003577:Cytochrome P-450 Enzyme System; C000607080:Cyp26a1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase; D002265:Carboxylic Ester Hydrolases; C022523:retinyl esterase