Wu C L, Melton D W
Institute of Cell and Molecular Biology, Edinburgh University, Scotland.
Nat Genet. 1993 Mar;3(3):235-40. doi: 10.1038/ng0393-235.
The inherited disease Lesch-Nyhan syndrome, which is caused by a deficiency of the enzyme hypoxanthine phosphoribosyltransferase (HPRT), is characterized by behavioural alterations, including self-injurious behaviour and mental retardation. Although HPRT-deficient mice have been generated using the embryonic stem cell system, no spontaneous behavioural abnormalities had been reported. We examined whether mice were more tolerant of HPRT deficiency because they were more reliant on adenine phosphoribosyltransferase (APRT) than HPRT for their purine salvage. The administration of an APRT inhibitor to HPRT-deficient mice induced persistent self-injurious behaviour. This combined genetic and biochemical model will facilitate the study of Lesch-Nyhan syndrome and the evaluation of novel therapies.
遗传性疾病莱施-奈恩综合征由次黄嘌呤磷酸核糖基转移酶（HPRT）缺乏引起，其特征为行为改变，包括自伤行为和智力迟钝。尽管已利用胚胎干细胞系统培育出HPRT缺陷小鼠，但此前尚无自发行为异常的报道。我们研究了小鼠是否因在嘌呤补救途径中比HPRT更依赖腺嘌呤磷酸核糖基转移酶（APRT）而对HPRT缺乏更具耐受性。给HPRT缺陷小鼠施用APRT抑制剂可诱导持续的自伤行为。这种遗传与生化相结合的模型将有助于莱施-奈恩综合征的研究及新疗法的评估。
