Gene basis high responding monkeys to cholesterol diet

本实验对猴作为高胆固醇血症动物模型的可行性进行了初步研究。用含0.1%胆固醇的猴粮喂养10只食蟹猴。两只猴子保持100 mg/dl的血清胆固醇水平。相比之下，两只基础水平约为200 mg/dl的猴子在4周后胆固醇水平显著升高至400 mg/dl。其他猴子表现出中等水平。这些猴子在胆固醇饮食前的水平与1、3、6周后的水平相关良好。本研究测定了503只日本猕猴和恒河猴的胆固醇水平，并分析了它们之间的亲缘关系。31个日本家系中有3个和26个恒河猴家系中有2个疑似高胆固醇血症。检测LDLR（低密度脂蛋白受体）基因。未发现恒河猴第6外显子无义突变。将LDLR分为9个区域，用LAPCR方法检测。1例高反应家系母猴的杂合子外显子12-14的DNA片段比正常猕猴短200 bp。我们正在进一步研究LDLR基因缺失的性质。猕猴的这一区域为2.7kb，而人的这一区域为3.4kb。我们将进一步研究LDLR和其他胆固醇代谢蛋白的基因结构。

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.