Batten, Matthew L.; Imanishi, Yoshikazu; Maeda, Tadao; Tu, Daniel C.; Moise, Alexander R.; Bronson, Darin; Possin, Daniel; Van Gelder, Russell N.; Palczewski, Krzysztof
citation_title
Lecithin-retinol acyltransferase is essential for accumulation of all-trans-retinyl esters in the eye and in the liver
citation_date
2004
Description
Lecithin-retinol acyltransferase (LRAT), an enzyme present mainly in the retinal pigmented epithelial cells and liver, converts all-trans-retinol into all-trans-retinyl esters. In the retinal pigmented epithelium, LRAT plays a key role in the retinoid cycle, a two-cell recycling system that replenishes the 11-cis-retinal chromophore of rhodopsin and cone pigments. We disrupted mouse Lrat gene expression by targeted recombination and generated a homozygous Lrat knock-out (Lrat-/-) mouse. Despite the expression of LRAT in multiple tissues, the Lrat-/- mouse develops normally. The histological analysis and electron microscopy of the retina for 6-8-week-old Lrat-/- mice revealed that the rod outer segments are approximately 35% shorter than those of Lrat+/+ mice, whereas other neuronal layers appear normal. Lrat-/- mice have trace levels of all-trans-retinyl esters in the liver, lung, eye, and blood, whereas the circulating all-trans-retinol is reduced only slightly. Scotopic and photopic electroretinograms as well as pupillary constriction analyses revealed that rod and cone visual functions are severely attenuated at an early age. We conclude that Lrat-/- mice may serve as an animal model with early onset severe retinal dystrophy and severe retinyl ester deprivation.
Type
text;
citation_publisher
American Society for Biochemistry and Molecular Biology (ASBMB)
citation_volume
279
citation_issue
11
citation_firstpage
10422
Citation_lastpage
10432
citation_keywords
Antibodies, Monoclonal; Chromatography, High Pressure Liquid; Microscopy, Fluorescence
Subject (MESH)
Acyltransferases; Esters; Electroretinography
citation_language
eng;
Bibliographic Citation
Batten ML, Imanishi Y, Maeda T, Tu DC, Moise AR, Bronson D, Possin D, Van Gelder RN, Baehr W, Palczewski K. (2004). Lecithin-retinol acyltransferase is essential for accumulation of all-trans-retinyl esters in the eye and in the liver. J Biol Chem, 279(11), 10422-32
Rights Management
(c)American Society for Biochemistry and Molecular Biology (ASBMB)
