PAHHPH-5 - A MOUSE MUTANT DEFICIENT IN PHENYLALANINE-HYDROXYLASE
PAHHPH-5 - A MOUSE MUTANT DEFICIENT IN PHENYLALANINE-HYDROXYLASE
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DOI：
10.1073/pnas.87.5.1965
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发表时间：
1990-03-01
影响因子：
11.1
通讯作者：
SHEDLOVSKY, A
中科院分区：
文献类型：
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作者：
MCDONALD, JD;BODE, VC;SHEDLOVSKY, A
表现出遗传性高苯丙氨酸血症的突变小鼠已被分离后，乙基亚硝基脲诱变的生殖系。我们描述了一个突变的家系，其中苯丙氨酸羟化酶活性是严重缺乏的纯合子和减少杂合子，而其他生化成分的苯丙氨酸羟化酶是正常的。在纯合子中，注射苯丙氨酸会引起严重的高苯丙氨酸血症和苯酮的尿排泄，但不会引起高酪氨酸血症。当突变型纯合子的饮用水中含有苯丙氨酸时，会产生严重的慢性高苯丙氨酸血症。遗传作图已将突变定位于小鼠10号染色体的Pah位点（苯丙氨酸羟化酶的结构基因）或其附近。这种突变体提供了一种有用的遗传动物模型，在相同的酶在人类苯丙酮尿症的影响。
Mutant mice exhibiting heritable hyperphenylalaninemia have been isolated after ethylnitrosourea mutagenesis of the germ line. We describe one mutant pedigree in which phenylalanine hydroxylase activity is severely deficient in homozygotes and reduced in heterozygotes while other biochemical components of phenylalanine catabolism are normal. In homozygotes, injection of phenylalanine causes severe hyperphenylalaninemia and urinary excretion of phenylketones but not hypertyrosinemia. Severe chronic hyperphenylalaninemia can be produced when mutant homozygotes are given phenylalanine in their drinking water. Genetic mapping has localized the mutation to murine chromosome 10 at or near the Pah locus, the structural gene for phenylalanine hydroxylase. This mutant provides a useful genetic animal model affected in the same enzyme as in human phenylketonuria.