Baboon Lecithin Cholesterol Acyltransferase (LCAT): cDNA sequences of two alleles, evolution, and gene expression

Hixson, James E.; Driscoll, Donna M.; Birnbaum, Shifra; Britten, Marjorie L.

doi:10.1016/0378-1119(93)90578-q

Cited by 15 publications

(8 citation statements)

References 10 publications

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“…In man, mouse, and rat, the liver is the predominant tissue of LCAT mRNA expression (20,57). Interestingly, one primate species, the baboon, has been reported to exhibit 3 times higher LCAT mRNA levels in brain than in liver of female animals (18); the authors observed similar results in male baboons. In all other studies so far, extrahepatic tissues were found to express only trace amounts of LCAT (20,57).…”

Section: Fig 3 Developmental Pattern Of Lcat Gene Expression In Chisupporting

confidence: 74%

“…The overall similarity at both the nucleotide and amino acid level of the avian enzyme with mammalian LCATs including those of man, baboon, rat, and mouse (17)(18)(19)(20) is striking. For instance, the chicken LCAT protein sequence is 73% identical with that of the human enzyme, and amino acids unequivocally involved in LCAT function are conserved.…”

Section: Molecularmentioning

confidence: 99%

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Chicken Lecithin-Cholesterol Acyltransferase

Hengstschläger-Ottnad

Kuchler

Schneider

1995

Journal of Biological Chemistry

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Rapidly growing oocytes in the laying hen are, in addition to the liver, targets of the so-called "reverse cholesterol transport" (RCT) (Vieira, P. M., Vieira, A. V., Sanders, E. J., Steyrer, E., Nimpf, J., and Schneider, W. J. (1995) J. Lipid Res. 36, 601-610), pointing to the importance of this process in nonplacental reproduction. We have begun to delineate the details of this unique transport pathway branch by molecular characterization of the first nonmammalian lecithin-cholesterol acyltransferase (LCAT), the enzyme that catalyzes an early step in RCT. The biological significance of the enzyme is underscored by the high degree of protein sequence identity (73%) maintained from chicken to man. Interestingly, the conservation extends much less to the cysteine residues; in fact, two of the cysteines thought to be important in mammalian enzymes (residues 31 and 184 in man) are absent from the chicken enzyme, providing proof of their dispensability for enzymatic activity. Antibodies prepared against a chicken LCAT fusion protein cross-react with human LCAT and identify a 64-kDa protein present in enzymatically active fractions obtained by hydrophobic chromatography of chicken serum. The developmental and tissue distribution pattern of LCAT in females is striking; during embryogenesis and adolescence, LCAT expression is extremely high in liver but undetectable in brain. Upon onset of laying, however, brain LCAT mRNA increases suddenly and is maintained at levels 5 times higher than in liver, in stark contrast to most mammals. In adult roosters, the levels of LCAT transcripts in brain are lower than in liver. Together with the molecular characterization of chicken LCAT, these newly discovered developmental changes and gender differences in its expression establish the avian oocyte/liver system as a powerful model to delineate in vivo regulatory elements of RCT.

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Section: Fig 3 Developmental Pattern Of Lcat Gene Expression In Chisupporting

confidence: 74%

Section: Molecularmentioning

confidence: 99%

Chicken Lecithin-Cholesterol Acyltransferase

Hengstschläger-Ottnad

Kuchler

Schneider

1995

Journal of Biological Chemistry

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“…Evaluation of amino acid sequence comparisons from other lipoprotein genes sequenced for both human and baboon show FIC1 is more highly conserved than many lipoprotein genes. For example, apo C-I contains 85.5% amino acid identity [23], apo E has 93.7% identity [10], apo A-I has 95.1% identity [9], LCAT has 98.4% identity [11], and lipoprotein lipase is the most highly conserved with 99.4% amino acid identity [5].…”

Section: Fic1 Baboon Vs Human Amino Acid Sequencementioning

confidence: 99%

The FIC1 gene: structure and polymorphisms in baboon

Cox

2002

J of Medical Primatology

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A genome scan performed on 648 pedigreed baboons to detect and localize quantitative trait loci (QTL) for lipoprotein phenotypes that are known risk factors for atherosclerosis indicated the presence of a QTL on chromosome 18q that exerts a major influence on HDL-cholesterol (HDL-C) related phenotypes. Inspection of the human gene map revealed that the familial intrahepatic cholestatis gene 1 (FIC1) maps to the homologous region of baboon chromosome 18 containing the major QTL influencing HDL-C phenotypes. FIC1 is a strong biological candidate for this QTL because HDL-C is the preferred precursor for bile acid synthesis. In this study, we cloned and sequenced FIC1 cDNA and found that it is highly conserved between human and baboon. We also sequenced FIC1 cDNAs from a panel of unrelated baboons revealing single nucleotide polymorphisms (SNPs) and a polymorphic dinucleotide repeat. None of the baboon SNPs corresponded to human FIC1 mutations associated with familial intrahepatic cholestasis or benign recurrent intrahepatic cholestasis disorders.

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“…Baboon and human apolipoprotein gene coding sequences are 90%-96% identical, and noncoding sequences are 85%-89% identical (Hixson et al 1988a(Hixson et al , 1988b(Hixson et al , 1993b(Hixson et al , 1996. Baboon and human LCAT and LPL, which encode lipid-metabolizing enzymes, are 97%-98% identical in their coding sequences (Hixson et al 1993a;Cole and Hixson 1995). Studies of apolipoprotein(a) (apo[a]), a component of the atherogenic lipoprotein (a) (Lp[a]) particle, in animal models have focused on baboons and other primates because the gene encoding apo(a) is not present in other laboratory animals (Rainwater et al 1989;Rainwater 1994).…”

Section: Atherosclerosismentioning

confidence: 99%