THE INFLUENCE OF GENETIC BACKGROUND ON THE EXPRESSION OF MUTATIONS AT THE DIABETES (DB) LOCUS IN THE MOUSE .6. HEPATIC MALIC ENZYME-ACTIVITY IS ASSOCIATED WITH DIABETES SEVERITY
THE INFLUENCE OF GENETIC BACKGROUND ON THE EXPRESSION OF MUTATIONS AT THE DIABETES (DB) LOCUS IN THE MOUSE .6. HEPATIC MALIC ENZYME-ACTIVITY IS ASSOCIATED WITH DIABETES SEVERITY
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DOI：
10.1016/0026-0495(92)90299-p
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发表时间：
1992-10-01
影响因子：
9.8
通讯作者：
COLEMAN, DL
中科院分区：
文献类型：
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作者：
COLEMAN, DL
由突变糖尿病（db）在小鼠中产生的糖尿病的严重程度是明显的品系依赖性。当db突变在C57BL KsJ（BKs）和DBA 2J菌株中保持时，观察到严重的糖尿病，而当它在C57BL J（B6）近交系背景中保持时，观察到轻度的、补偿良好的糖尿病。我们对苹果酸酶活性调节的研究表明，BK和DBA 2J菌株都在苹果酸酶调节（Modlr）位点上携带B等位基因，并且具有低酶活性，而B6菌株携带a等位基因，并且苹果酸酶活性是BK和DBA 2J菌株中所见的2 - 3倍。为了评估苹果酸酶活性在调节糖尿病严重程度中的任何作用，我们使用BKs-db/+和B6-db/+小鼠作为祖细胞产生了F2代糖尿病小鼠。F2代雄性糖尿病小鼠根据糖尿病严重程度分为三组。在这三组中观察到的糖尿病严重程度和苹果酸酶活性之间的一致性表明，调节苹果酸酶活性的基因（或紧密连锁的基因）的主要作用是负责在小鼠中观察到的db突变的遗传背景效应。
The severity of diabetes produced by the mutation diabetes (db) in the mouse is markedly strain-dependent. When the db mutation is maintained in the C57BL KsJ (BKs) and DBA 2J strains, severe diabetes is observed, whereas when it is maintained in the C57BL J (B6) inbred background, a mild, well-compensated diabetes is observed. Our studies on the regulation of malic enzyme activity showed that both the BKs and DBA 2J strains carried the b allele at the malic enzyme regulatory (Modlr) locus and had low enzyme activity, while the B6 strains carried the a allele and had malic enzyme activity two to three times that seen in the BKs and DBA 2J strains. To assess any role of malic enzyme activity in modulating diabetes severity, we produced an F2 generation of diabetic mice using BKs-db/+ and B6-db/+ mice as progenitors. Male diabetic mice of the F2 generation segregated into three groups with respect to diabetes severity. The concordance observed between diabetes severity and malic enzyme activity seen in these three groups suggests a major role for a gene (or a closely linked gene) regulating malic enzyme activity to be responsible for much of the genetic background effects observed with the db mutation in the mouse.