ARRAY SCREENING FOR LESCH NYHAN DISEASE

描述(摘自申请者摘要)：Lesch Nyhan病(LND)是 该基因突变引起的令人费解的神经发育障碍 编码嘌呤挽救途径酶的次黄嘌呤鸟嘌呤 磷酸核糖转移酶(HPRT)。这种障碍包括精神发育迟缓， 高尿酸血症、舞蹈运动障碍和非自愿和强迫性自残。 HPRT基因表达缺陷在神经表型中的作用是 人们对此知之甚少，但通常认为与减少 纹状体中的多巴胺含量和多巴胺摄取。我们知道的很少 关于HPRT缺乏导致基底节的机制 多巴胺缺陷与神经表型的关系。在这个探索性的 申请，调查人员建议通过以下方式审查这一中心问题 高密度微阵列和DNA探针的应用研究进展 用于识别其表达受影响的基因和基因家族的芯片 HPRT缺乏症。他们提出的研究基于以下证据： 1.多巴胺缺陷是神经学表型中的原因。 2.嘌呤代谢、氧化应激及相关基因的表达和反应 神经营养因子参与了HPRT-多巴胺的相互作用。 3.筛选和芯片阵列筛选可以识别单个基因和模式。 其表达受HPRT表达调控的基因。

DESCRIPTION (adapted from applicant's abstract): Lesch Nyhan disease (LND) is a puzzling neurological developmental disorder caused by mutations in the gene encoding the purine salvage pathway enzyme hypoxanthine guanine phosphoribosyltransferase (HPRT). The disorder includes mental retardation, hyperuricemia, choreoathetosis and involuntary and compulsive self-mutilation. The role of deficient HPRT gene expression in the neurological phenotype is poorly understood, but is generally thought to be related to a reduction of dopamine content and dopamine uptake in the striatum. Very little is known regarding the mechanisms by which HPRT deficiency leads to the basal ganglion dopamine defects and to the neurological phenotype. In this exploratory application, the investigators propose to examine this central question by applying state-of-the-art screening of high density microarrays and DNA probe chips to identify genes and families of genes whose expression is affected by HPRT deficiency. Their proposed studies are based on evidence that: 1. the dopamine defect is causal in the neurological phenotype. 2. genes of purine metabolism, oxidative stress and expression of and response to neurotrophic factors are involved in the HPRT-dopamine interaction. 3. filter and chip array screening can identify individual genes and patterns of genes whose expression is modulated by HPRT expression.