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J. Biol. Chem., Vol. 280, Issue 48, 40226-40234, December 2, 2005

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Disruption of the Lecithin:Retinol Acyltransferase Gene Makes Mice More Susceptible to Vitamin A Deficiency^*

From the Department of Pharmacology, Weill Medical College of Cornell University, New York, New York 10021

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 µM in WT mice versus 0.13 ± 0.06 µM 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.

Received for publication, September 1, 2005 , and in revised form, September 15, 2005.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by National Institutes of Health Cancer Pharmacology Training Grant 5T32CA62948.

² To whom correspondence should be addressed: Dept. of Pharmacology, Weill Medical College of Cornell University, 1300 York Ave., New York, NY 10021. Tel.: 212-746-6250; Fax: 212-746-8858; E-mail: ljgudas{at}med.cornell.edu.

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