Tissue-specific expression, developmental regulation, and chromosomal mapping of the lecithin: cholesterol acyltransferase gene. Evidence for expression in brain and testes as well as liver.
Lecithin:cholesterol acyltransferase (LCAT) catalyzes the esterification of cholesterol in high density lipoproteins, thereby facilitating transport of excess cholesterol from peripheral tissues to liver. We report here studies of the developmental, dietary, and genetic control of LCAT gene expression. In adult male Sprague-Dawley rats fed a standard chow diet LCAT mRNA was most abundant in liver, a major source of the plasma enzyme, but appreciable levels were also present in brain and testes. Since both brain and testes are isolated from blood by tight cellular barriers, undoubtedly greatly reducing the level of plasma-derived LCAT in cerebrospinal fluid and testes, the production of LCAT in these tissues may be important for removal of excess cholesterol. Noteworthy changes in the expression of LCAT mRNA were observed during development of both rodents and humans. On the other hand, LCAT mRNA levels were relatively resistant to dietary challenge or to drugs affecting cholesterol metabolism. Since human epidemiological studies have suggested an association between LCAT levels and variations of high density lipoprotein cholesterol, we examined LCAT gene polymorphisms in a mouse animal model. Mapping of the LCAT gene (Lcat) to mouse Chromosome 8 within 2 centimorgans of the Es-2 locus indicates that it does not correspond to any previously mapped loci affecting high density lipoprotein phenotypes in the mouse.
Warden
C H
CH
Department of Medicine, University of California, Los Angeles 90024.
Langner
C A
CA
Gordon
J I
JI
Taylor
B A
BA
McLean
J W
JW
Lusis
A J
AJ
D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000201:enzymology / Q000254:growth & development*; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D003001:Cloning, Molecular; D004032:Diet; D005314:Embryonic and Fetal Development; D005260:Female; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic; D015723:Gene Library; D005796:Genes; D006801:Humans; D008099:Liver / Q000196:embryology / Q000201:enzymology / Q000254:growth & development*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009928:Organ Specificity; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013737:Testis / Q000196:embryology / Q000201:enzymology / Q000254:growth & development*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D007862:Phosphatidylcholine-Sterol O-Acyltransferase