Patejunas G, Bradley A, Beaudet A L, O'Brien W E
Institute for Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030.
Somat Cell Mol Genet. 1994 Jan;20(1):55-60. doi: 10.1007/BF02257486.
Argininosuccinate synthetase (ASS) is a urea cycle enzyme that forms argininosuccinate from citrulline and aspartate. Mutations at the ASS locus in man cause the inherited disease, citrullinemia. Citrullinemia is inherited as an autosomal recessive trait and is characterized, biochemically, by elevated levels of blood citrulline and ammonia and often results in early neonatal death if untreated. We have used homologous recombination in embryonic stem cells to generate a line of mice having a targeted disruption of the Ass gene. Homozygous mutant animals develop high levels of blood citrulline, become hyperammonemic, and die within one or two days after birth. Because the phenotype of the mutant mice closely resembles that of humans who lack the ASS enzyme, we expect that these mice will serve as a useful model for exploring new treatments for citrullinemia including somatic gene therapy.
精氨琥珀酸合成酶（ASS）是一种尿素循环酶，可由瓜氨酸和天冬氨酸形成精氨琥珀酸。人类ASS基因座的突变会导致遗传性疾病——瓜氨酸血症。瓜氨酸血症以常染色体隐性特征遗传，其生化特征是血液中瓜氨酸和氨水平升高，如果不治疗，通常会导致新生儿早期死亡。我们利用胚胎干细胞中的同源重组技术，培育出了一系列Ass基因被靶向破坏的小鼠品系。纯合突变动物血液中的瓜氨酸水平很高，会出现高氨血症，并在出生后一到两天内死亡。由于突变小鼠的表型与缺乏ASS酶的人类非常相似，我们预计这些小鼠将成为探索包括体细胞基因治疗在内的瓜氨酸血症新疗法的有用模型。
