Gene basis high responding monkeys to cholesterol diet

初步研究了猴子作为高胆固醇血症动物模型的可能性。10只吃螃蟹的猴子被喂食含有0.1%胆固醇的猴子饲料。两只猴子保持100毫克/分升的血清胆固醇水平。相比之下，基础水平在200mg/dl左右的两只猴子在4周后胆固醇水平显著升高至400mg/dl。其他猴子则表现出中等水平。这些猴子在胆固醇饮食前的水平与1、3、6周后的水平密切相关。这一结果表明，我们可以通过调查正常饮食的猴子的胆固醇水平来发现高反应的猴子。我们测量了503只日本猕猴和恒河猴的胆固醇水平，并分析了家族关系。31个日本家族中有3个，26个恒河家族中有2个存在高胆固醇血症的嫌疑。检测低密度脂蛋白受体（LDLR）基因。没有恒河猴报道的6外显子无义突变。LDLR分为9个区域，采用LAPCR法进行检测。高反应家族的一只母恒河猴杂合子外显子12-14的DNA区域比正常猕猴短200bp。我们正在进一步研究LDLR基因缺失的本质。猕猴的这一区域为2.7 kb，而人类的这一区域为3.4 kb。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.