At least six forms of extremely homologous cytochromes P-450 in rat liver are encoded at two closely linked genetic loci.
At least six forms of extremely homologous cytochromes P-450 in rat liver are encoded at two closely linked genetic loci.
复制标题
大鼠肝脏中至少六种极其同源的细胞色素 P-450 在两个紧密相连的遗传位点编码。
DOI：
--
复制
发表时间：
1983
影响因子：
11.1
通讯作者：
F. Walz
中科院分区：
文献类型：
--
作者：
A. Rampersaud;F. Walz
大鼠肝脏中苯巴比妥诱导的细胞色素P-450亚群已被证明由四种密切相关的酶形式组成，这些酶似乎与菌株相关。在本研究中，多肽组成这个家庭进行了分析，从64个苯巴比妥治疗的大鼠肝微粒体的二维电泳。调查的动物包括两种性别的4个近交系和5个远交系/殖民地和F1后代从10个杂交。根据其独特的电泳行为和肽图鉴定了该多肽家族的两个新成员。观察到8种表型，由2至4个成员多肽组成。发现6个密切相关的细胞色素P-450由两个遗传位点编码，其中P-450 b位点至少有4个等位基因，P-450 e位点至少有2个等位基因。远交品系的大多数菌落的特点是在一个或两个这些位点的多态性，在任何情况下，他们不包含独特的等位基因。对亲本及其F1后代的分析表明，P-450 b和P-450 e基因座在同一常染色体上紧密连锁，并以共显性方式表达。此外，这些基因座的产物似乎是协同调节的。P-450 b和P-450 e基因之间的高度同源性、高度多态性和紧密连锁表明，它们受到与其他多基因家族中保持这些特征相同的遗传机制的影响。
A subpopulation of phenobarbital-induced cytochrome P-450 in rat liver has been shown to consist of four closely related forms of the enzyme that appeared to be strain-related. In the present study, polypeptides composing this family were analyzed by two-dimensional electrophoresis of hepatic microsomes from 64 individual phenobarbital-treated rats. The animals surveyed included both sexes from four inbred and five outbred strains/colonies and F1 progenies from 10 crosses. Two new members of this polypeptide family were identified on the basis of their unique electrophoretic behavior and peptide maps. Eight phenotypes were observed that consisted of two to four member polypeptides. The six closely related cytochromes P-450 were found to be encoded at two genetic loci with at least four alleles at the P-450b locus and at least two alleles at the P-450e locus. Most colonies of outbred strains were characterized by polymorphism at one or both of these loci, and in no case did they contain unique alleles. Analyses of parents and their F1 progenies indicated that the P-450b and P-450e loci are closely linked on the same autosome and are expressed codominantly. Furthermore, the products of these loci appear to be coordinately regulated. The extreme homology between P-450b and P-450e genes, their high degree of polymorphism, and their close linkage suggest that they are subject to the same genetic mechanisms that maintain these features in other multigene families.