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PMID: 14684738 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Lecithin-retinol acyltransferase is essential for accumulation of all-trans-retinyl esters in the eye and in the liver.

The Journal of biological chemistry ·Vol. 279 ·No. 11 ·2004-03-12 ·Pages 10422-32

Batten ML, Imanishi Y, Maeda T, Tu DC, Moise AR, Bronson D, Possin D, Van Gelder RN, Baehr W, Palczewski K

Abstract

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.

MeSH Terms
Acyltransferases/metabolism,physiology Animals Antibodies, Monoclonal/metabolism Chromatography, High Pressure Liquid DNA, Complementary/metabolism Electroretinography Esters/metabolism Eye/metabolism Genetic Vectors Genotype Homozygote Immunohistochemistry Kinetics Liver/metabolism Mice Mice, Knockout Mice, Transgenic Microscopy, Electron Microscopy, Fluorescence Models, Genetic Photons Retina/ultrastructure Retinoids/metabolism Rhodopsin/chemistry,metabolism Time Factors Tissue Distribution
Chemicals
Antibodies, Monoclonal DNA, Complementary Esters Retinoids Rhodopsin Acyltransferases lecithin-retinol acyltransferase
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Batten Matthew L
Department of Ophthalmology, University of Washington, Seattle, Washington 98195, USA.
Imanishi Yoshikazu
Maeda Tadao
Tu Daniel C
Moise Alexander R
Bronson Darin
Possin Daniel
Van Gelder Russell N
Baehr Wolfgang
Palczewski Krzysztof
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M312410200
Published
2004-03-12
Epub
2003-00-18
Pages
10422-32
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC1351249
Subset
IM
Grants
NEI NIH HHS · R01 EY014988 · United States
NEI NIH HHS · R01 EY009339 · United States
NEI NIH HHS · EYK0800403 · United States
NEI NIH HHS · EY14988 · United States
NEI NIH HHS · EY08123 · United States
NEI NIH HHS · EY09339 · United States
NEI NIH HHS · EY13385 · United States
NEI NIH HHS · R01 EY008123 · United States
NEI NIH HHS · R01 EY013385 · United States
External Links
PubMed source DOI: 10.1074/jbc.M312410200 PMC Full Text View journal details
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