Functional polymorphisms of the Lss and Fdft1 genes in laboratory rats
Functional polymorphisms of the Lss and Fdft1 genes in laboratory rats
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DOI：
10.1538/expanim.56.93
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发表时间：
2007-04-01
影响因子：
2.4
通讯作者：
Higuchi, Keiichi
中科院分区：
文献类型：
--
作者：
Mori, Masayuki;Sawashita, Jinko;Higuchi, Keiichi
我们之前发现了羊毛甾醇合成酶（Lss）和法尼基二磷酸法尼基转移酶I （Fdft1）基因的突变等位基因，它们在胆固醇生物合成途径中起作用，是SCR大鼠菌株遗传性白内障的决定因素。Lss(s)和Fdft1(s)为亚型等位基因，存在错义核苷酸替换，Lss(1)为空等位基因，存在核苷酸缺失/插入突变。在这里，我们报告了大鼠Lss和Fdft1基因的更详细的特征。对不同实验室大鼠菌株的筛选表明，低形态Lss(s)和Fdft1(s)等位基因不是SCR菌株所特有的，但在其他实验室大鼠菌株中广泛存在。同时，在所有大鼠品系中均未发现Lss(1)。研究还发现，在Lss上游调控区存在功能性菌株间多态性。在需要合成胆固醇的条件下，BN菌株比ACI和SCR具有更高的表达lless转录本的潜力。在需要停止胆固醇合成的情况下，SCR抑制Lss转录的效率低于BN和ACI。这些发现不仅暗示了实验室大鼠胆固醇稳态存在遗传多态性，而且还指出了具有不同lless等位基因的大鼠品系对干预胆固醇代谢的措施表现出不同反应的可能性。
We previously identified mutant alleles of the lanosterol synthase (Lss) and farnesyl diphosphate farnesyl transferase I (Fdft1) genes, which function in the cholesterol biosynthesis pathway, as determinants for hereditary cataracts in the SCR rat strain. Lss(s) and Fdft1(s) were established as hypomorphic alleles with missense nucleotide substitutions, while Lss(1) is a null allele with nucleotide deletion/insertion mutations. Here we report a more detailed characterization of the rat Lss and Fdft1 genes. Screening of various laboratory rat strains revealed that the hypomorphic Lss(s) and Fdft1(s) alleles are not specific to the SCR strain, but are widely prevalent in other laboratory rat strains. Meanwhile, Lss(1) was not found in any rat strains examined. It was also found that functional inter-strain polymorphisms are present in the Lss upstream regulatory region. The BN strain had a higher potential for expression of Lss transcripts than ACI and SCR under conditions where cholesterol synthesis is necessary. SCR was less efficient than BN and ACI in suppressing Lss transcription in circumstances when cholesterol synthesis should be halted. These findings not only imply that there is a genetic polymorphism for cholesterol homeostasis in laboratory rats, but also point to the possibility that rat strains with different Lss alleles exhibit different responses to measures intervening in cholesterol metabolism.