IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ruiz, A.
Right arrow Articles by Bok, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ruiz, A.
Right arrow Articles by Bok, D.
(Investigative Ophthalmology and Visual Science. 2001;42:31-37.)
© 2001 by The Association for Research in Vision and Ophthalmology, Inc.

Genomic Organization and Mutation Analysis of the Gene Encoding Lecithin Retinol Acyltransferase in Human Retinal Pigment Epithelium

Alberto Ruiz1, Markus H. Kuehn2, Jeaneen L. Andorf2, Edwin Stone2, Gregory S. Hageman2 and Dean Bok1,3,4

1 From the Department of Neurobiology, 2 Brain Research Institute and 3 Jules Stein Eye Institute, School of Medicine, University of California, Los Angeles; and the 4 Department of Ophthalmology and Visual Sciences, The University of Iowa, Center for Macular Degeneration, Iowa City.

PURPOSE. To determine the structure of the human lecithin retinol acyltransferase (LRAT) gene, map its chromosomal localization, and screen for mutations in humans with various hereditary retinal degenerations.

METHODS. Using DNA probes specific for LRAT, a bacterial artificial chromosome (BAC) clone containing the LRAT gene was isolated, subcloned into DNA fragments and relevant subclones characterized by sequencing. Exon–intron junctions were determined by comparison with the cDNA sequence previously published. Southern blot analysis was performed on human genomic DNA samples digested with several restriction enzymes. Fluorescence in situ hybridization (FISH) analysis of normal metaphase chromosomes derived from phytohemagglutinin (PHA) stimulated peripheral blood lymphocytes and radiation hybrid mapping were used for localization of the LRAT gene. Single-strand conformation polymorphism analysis (SSCP) was used to screen for potential mutations in patients with age-related macular degeneration, Leber congenital amaurosis, retinitis pigmentosa, and cone-rod dystrophy.

RESULTS. The human LRAT gene is organized into three exons of 219, 541, and 2058 bp and two introns of 103 and 4117 bp. Southern blot analysis of digested genomic DNA revealed a single band, suggesting a single copy of the LRAT gene. The human LRAT gene was localized to chromosome 4q31.2, a locus having no previous association with human eye disease. Additionally, the bovine LRAT homologue sequence was deduced and a general LRAT protein topology is suggested. No polymorphisms that segregated with retinal disease phenotypes were identified in 374 unrelated probands.

CONCLUSIONS. The organization of the LRAT gene, based on cDNA clones derived from the retinal pigment epithelium (RPE) has been determined. Its structure is less complex than other acyltransferases such as lecithin cholesterol acyltransferase (LCAT) and acyl CoA acyltransferase (ACAT). The absence of polymorphisms in the probands examined suggests a very low mutation level in the LRAT gene from the diseases analyzed.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
A. R. Moise, M. Golczak, Y. Imanishi, and K. Palczewski
Topology and Membrane Association of Lecithin: Retinol Acyltransferase
J. Biol. Chem., January 19, 2007; 282(3): 2081 - 2090.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
D. P. Simmons, M. L. Peach, J. R. Friedman, M. M.B. Green, M. C. Nicklaus, and L. M. De Luca
Evidence that sequence homologous region in LRAT-like proteins possesses anti-proliferative activity and DNA binding properties: translational implications and mechanism of action
Carcinogenesis, April 1, 2006; 27(4): 693 - 707.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. Boorjian, S. K. Tickoo, N. P. Mongan, H. Yu, D. Bok, R. R. Rando, D. M. Nanus, D. S. Scherr, and L. J. Gudas
Reduced Lecithin: Retinol Acyltransferase Expression Correlates with Increased Pathologic Tumor Stage in Bladder Cancer
Clin. Cancer Res., May 15, 2004; 10(10): 3429 - 3437.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. L. Batten, Y. Imanishi, T. Maeda, D. C. Tu, A. R. Moise, D. Bronson, D. Possin, R. N. Van Gelder, W. Baehr, and K. Palczewski
Lecithin-retinol Acyltransferase Is Essential for Accumulation of All-trans-Retinyl Esters in the Eye and in the Liver
J. Biol. Chem., March 12, 2004; 279(11): 10422 - 10432.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
A. C. Ross and R. Zolfaghari
Regulation of Hepatic Retinol Metabolism: Perspectives from Studies on Vitamin A Status
J. Nutr., January 1, 2004; 134(1): 269S - 275.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
A. C. Ross
Retinoid Production and Catabolism: Role of Diet in Regulating Retinol Esterification and Retinoic Acid Oxidation
J. Nutr., January 1, 2003; 133(1): 291S - 296.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
D. P. Simmons, F. Andreola, and L. M. De Luca
Human melanomas of fibroblast and epithelial morphology differ widely in their ability to synthesize retinyl esters
Carcinogenesis, November 1, 2002; 23(11): 1821 - 1830.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2001 by the Association for Research in Vision and Ophthalmology