BRAIN PURINES IN A GENETIC MOUSE MODEL OF LESCH-NYHAN DISEASE
BRAIN PURINES IN A GENETIC MOUSE MODEL OF LESCH-NYHAN DISEASE
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DOI：
10.1111/j.1471-4159.1993.tb03488.x
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发表时间：
1993-06-01
影响因子：
4.7
通讯作者：
FRIEDMANN, T
中科院分区：
文献类型：
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作者：
JINNAH, HA;PAGE, T;FRIEDMANN, T
最近已经产生了在编码嘌呤补救酶次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HPRT）的基因中携带突变的小鼠，以提供Lesch-Nyhan病的动物模型。目前的研究进行了表征HPRT的表达突变的后果，并在这些突变体中的脑嘌呤含量的潜在变化的特点。我们的研究结果表明，突变体动物没有检测到HPRT免疫反应性物质的蛋白质印迹和脑组织匀浆中没有检测到HPRT酶活性，确认它们是完全HPRT缺陷（HPRT）。尽管没有HPRT介导的嘌呤补救，动物具有明显正常的脑嘌呤含量。然而，从头嘌呤合成，如通过[C-14]甲酸盐掺入脑嘌呤所测量的，在突变动物中加速四到五倍。嘌呤合成的这种增加可以保护HPRT-小鼠免受脑嘌呤的潜在消耗，尽管HPRT介导的嘌呤补救完全受损。
Mice carrying a mutation in the gene encoding the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) have recently been produced to provide an animal model for Lesch-Nyhan disease. The current studies were conducted to characterize the consequences of the mutation on the expression of HPRT and to characterize potential changes in brain purine content in these mutants. Our results indicate that the mutant animals have no detectable HPRT-immunoreactive material on western blots and no detectable HPRT enzyme activity in brain tissue homogenates, confirming that they are completely HPRT deficient (HPRT). Despite the absence of HPRT-mediated purine salvage, the animals have apparently normal brain purine content. However, de novo purine synthesis, as measured by [C-14]formate incorporation into brain purines, is accelerated four- to fivefold in the mutant animals. This increase in the synthesis of purines may protect the HPRT- mice from potential depletion of brain purines despite complete impairment of HPRT-mediated purine salvage.