Suto Jun-ichi, Takahashi Yuji, Sekikawa Kenji
Department of Molecular Biology and Immunology, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602, Japan.
Biochem Genet. 2004 Oct;42(9-10):347-63. doi: 10.1023/b:bigi.0000039809.40228.d3.
A highly significant cholesterol quantitative trait locus (QTL) (Cq6) was identified on chromosome 1 in C57BL/6J x RR F2 mice. The Cq6 was located over the gene for apolipoprotein A-Il (Apoa2), and the RR allele was associated with increased plasma cholesterol. C57BL/6J has Apoa2a alleles and RR has Apoa2b alleles. Three different Apoa2 alleles are known on the basis of amino acid substitutions at four residues. Analysis with partial Apoa2 congenic strains possessing Apoa2a, Apoa2b, and Apoa2C alleles revealed that the Apoa2b allele is unique in the ability to increase cholesterol among the three Apoa2 alleles, and that the Ala-to-Val substitution at residue 61 may be crucial as far as cholesterol metabolism is concerned. We also investigated the question of whether the Apoa1 gene is responsible for the cholesterol QTLs (Cq4 and Cq5) that had been identified previously on chromosome 9 in C57BL/6J x KK-Ay/a F2 and in KK x RR F2, but not in C57BL/6J x RR F2 mice. Similar to Apoa2 alleles, three different Apoal alleles with two successive amino acid substitutions were revealed among the strains. However, we could not correlate Apoal polymorphisms with the occurrence of QTLs in these three sets of F2 mice.
在C57BL/6J×RR F2小鼠的1号染色体上鉴定出一个高度显著的胆固醇数量性状基因座（QTL）（Cq6）。Cq6位于载脂蛋白A-II（Apoa2）基因上方，RR等位基因与血浆胆固醇升高有关。C57BL/6J具有Apoa2a等位基因，RR具有Apoa2b等位基因。根据四个残基处的氨基酸替换，已知三种不同的Apoa2等位基因。对携带Apoa2a、Apoa2b和Apoa2C等位基因的部分Apoa2近交系进行分析发现，Apoa2b等位基因在三种Apoa2等位基因中具有独特的增加胆固醇的能力，就胆固醇代谢而言，第61位残基的丙氨酸到缬氨酸替换可能至关重要。我们还研究了Apoa1基因是否与先前在C57BL/6J×KK-Ay/a F2和KK×RR F2的9号染色体上鉴定出的胆固醇QTL（Cq4和Cq5）有关，但在C57BL/6J×RR F2小鼠中未鉴定出。与Apoa2等位基因类似，在这些品系中发现了三种不同的Apoa1等位基因，它们有两个连续的氨基酸替换。然而，我们无法将Apoa1多态性与这三组F2小鼠中QTL的出现相关联。
