加利福尼亚大学分子遗传中心和圣地亚哥医学院的一项研究表明，一种叫HPRT的基因对促使人类原始细胞转变成大脑正常的神经细胞的过程具有重要的作用。这种代谢基因就是总所周知的管家基因（housekeeping genes）。这项研究结果发布在Molecular Therapy杂志的在线版本上。
很多情况下，大部分细胞中的管家基因都是表达的。这些基因简单的代谢功能可以调控正常的代谢，或者说在基因没有起到合适作用时会导致严重的疾病。但是目前还没有关于这种基因与通路形成的关系的研究，通路决定干细胞和其他的原始细胞变成神经细胞，肌肉细胞，骨细胞或血细胞。
研究表明，HPRT承担了一个重要的新角色，即会导致路径中错误的产生，结果使得大量转录因子基因表达时高时低，而且许多表达是错误的。此外，在除了HPRT的许多其他的管家基因中，同样发现了一些基因可以调控正在形成的重要通路。
科研人员还对HPRT基因做了直接的试验证实，通过对莱施-尼汉疾病（Lesch Nyhan disease）严重神经紊乱的形成研究，表明HPRT基因确实可能导致神经学上的问题。而这些问题会直接影响出生和神经元的功能，尤其是对多巴胺依赖的神经传导神经元。(生物谷Bioon.com)
生物谷推荐原始出处：
Molecular Therapy (2009); doi:10.1038/mt.2009.178
Deficiency of the Housekeeping Gene Hypoxanthine–Guanine Phosphoribosyltransferase (HPRT) Dysregulates Neurogenesis
Ghiabe-Henri Guibinga1, Stephen Hsu1 and Theodore Friedmann1
1 Department of Pediatrics, Center for Molecular Genetics, University of California, San Diego School of Medicine, La Jolla, California, USA
Neuronal transcription factors play vital roles in the specification and development of neurons, including dopaminergic (DA) neurons. Mutations in the gene encoding the purine biosynthetic enzyme hypoxanthine–guanine phosphoribosyltransferase (HPRT) cause the resulting intractable and largely untreatable neurological impairment of Lesch–Nyhan disease (LND). The disorder is associated with a defect in basal ganglia DA pathways. The mechanisms connecting the purine metabolic defect and the central nervous system (CNS) phenotype are poorly understood but have been presumed to reflect a developmental defect of DA neurons. We have examined the effect of HPRT deficiency on the differentiation of neurons in the well-established human (NT2) embryonic carcinoma neurogenesis model. We have used a retrovirus expressing a small hairpin RNA (shRNA) to knock down HPRT gene expression and have examined the expression of a number of transcription factors essential for neuronal differentiation and marker genes involved in DA biosynthetic pathway. HPRT-deficient NT2 cells demonstrate aberrant expression of several transcription factors and DA markers. Although differentiated HPRT-deficient neurons also demonstrate a striking deficit in neurite outgrowth during differentiation, resulting neurons demonstrate wild-type electrophysiological properties. These results represent direct experimental evidence for aberrant neurogenesis in HPRT deficiency and suggest developmental roles for other housekeeping genes in neurodevelopmental disease.
