1996 Fiscal Year Final Research Report Summary
Gene basis high responding monkeys to cholesterol diet
| Project/Area Number |
07680683
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
TAKENAKA Osamu Kyoto University, Primate Research Institute, Professor, 霊長類研究所, 教授 (00093261)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Cholesterol / High responder to cholesterol diet / Primates / Animal model / Macaques / LDL receptor / Gene basis for disease / Lipid metabolism |
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| Research Abstract |
Preliminary experiment was conducted to examine possibilities of monkeys as animal model for hypercholestrolemia. Ten crab-eating monkeys were fed with monkey chow including 0.1% cholesterol. Two monkeys kept 100mg/dl of serum cholesterol level. In contrast, two monkeys of which basal level was around 200mg/dl showed remarkable elevation of cholesterol level to 400mg/dl after 4 weeks. The other monkeys showed the intermediate levels. The levels of those monkeys before cholesterol diet correlated well with those levels after 1,3,6 weeks. This result indicated that we can find out high responding monkeys by survey of the cholesterol levels of the monkeys of normal diet.
We measured the cholesterol levels of 503 Japanese and rhesus macaques and analyzed familial relationship. Three Japanese families out of 31 and 2 rhesus families out of 26 showed the doubt of hypercholesterolemia. The gene for LDLR (low density lipoprotein receptor) was examined. There were no macaques having nonsense mutation in exon 6 which was reported for rhesus macaques. LDLR was divided into 9 regions and examined by LAPCR method. One mother rhesus monkey of high responding family has shorter DNA region of exon 12-14 in heterozygote by 200bp than normal macaques. We are investigating further the nature of deletion in LDLR genes. This regions of macaques are 2.7 kb while that of human is 3.4 kb. We will further investigate the gene structure of LDLR and other cholesterol metabolizing proteins.
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