Variable expression of hepatic glucokinase in mice is due to a regulational locus that cosegregates with the glucokinase gene.

Variable expression of hepatic glucokinase in mice is due to a regulational locus that cosegregates with the glucokinase gene.
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小鼠中肝葡萄糖激酶的可变表达是由于与葡萄糖激酶基因共分离的调节位点所致。

DOI:
10.1006/geno.1997.4936
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发表时间:
1997
期刊:
Genomics.
影响因子:
--
通讯作者:
Magnuson,MA
Magnuson,MA
中科院分区:
--
文献类型:
--
作者:
Moates,JM;Postic,C;Decaux,JF;Girard,J;Magnuson,MA

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Gk活性位点影响小鼠肝组织葡萄糖激酶(GK)的表达。对小鼠GK基因座位内的微卫星分析显示,在22个近交系中,19个近交系中有两种主要单倍型,预示着肝脏GK基因的高表达或低表达。高活性品系C3H/HeJ小鼠和另外两个来自野生的品系含有不太常见的单倍型。在具有代表性的高和低Gk活性菌株的肝脏GK编码序列中没有发现编码序列的差异,从而排除了动力学异常作为肝脏GK活性差异的基础。通过限制性内切酶指纹-单链构象分析筛选∼10kb的潜在调控DNA,包括所有8个已知的DNA I超敏位点和4个新发现的DNA I超敏位点中的3个,发现了一个四核苷酸微卫星,其长度也可以预测Gk活性表型。这个四核苷酸重复序列位于肝脏转录单位的第一个内含子,靠近一个新发现的肝脏特异性DNA酶I超敏位点。这些结果表明,GK活性等位基因是与GK基因相关的一个调节基因座。
TheGk activitylocus affects expression of hepatic glucokinase (GK) in mice. Analysis of microsatellites within the mouse GK gene locus revealed two major haplotypes in 19 of 22 inbred strains predictive of either high or low hepatic GK gene expression. C3H/HeJ mice, a high-activity strain, and two other wild-derived strains contain less common haplotypes. No coding sequence differences were found in hepatic GK-coding sequences from representative high and lowGk activitystrains, thereby excluding kinetic abnormalities as the basis for hepatic GK activity differences. Screening of ∼10 kb of potential regulatory DNA, including all eight known and three of four newly identified DNase I-hypersensitive sites, by restriction enzyme fingerprinting–single-strand conformation analysis revealed a tetranucleotide microsatellite, the length of which was also predictive of theGk activityphenotype. This tetranucleotide repeat is located in the first intron of the hepatic transcription unit and lies close to a newly identified liver-specific DNase I-hypersensitive site. These results indicate that theGk activityalleles are a regulational locus associated with the GK gene locus.
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