加利福尼亞大學(xué)分子遺傳中心和圣地亞哥醫(yī)學(xué)院的一項(xiàng)研究表明,，一種叫HPRT的基因?qū)Υ偈谷祟愒技?xì)胞轉(zhuǎn)變成大腦正常的神經(jīng)細(xì)胞的過程具有重要的作用。這種代謝基因就是總所周知的管家基因（housekeeping genes）,。這項(xiàng)研究結(jié)果發(fā)布在Molecular Therapy雜志的在線版本上,。
很多情況下，大部分細(xì)胞中的管家基因都是表達(dá)的,。這些基因簡單的代謝功能可以調(diào)控正常的代謝,，或者說在基因沒有起到合適作用時會導(dǎo)致嚴(yán)重的疾病。但是目前還沒有關(guān)于這種基因與通路形成的關(guān)系的研究,，通路決定干細(xì)胞和其他的原始細(xì)胞變成神經(jīng)細(xì)胞，肌肉細(xì)胞,，骨細(xì)胞或血細(xì)胞。
研究表明,，HPRT承擔(dān)了一個重要的新角色，即會導(dǎo)致路徑中錯誤的產(chǎn)生,，結(jié)果使得大量轉(zhuǎn)錄因子基因表達(dá)時高時低,，而且許多表達(dá)是錯誤的,。此外，在除了HPRT的許多其他的管家基因中,，同樣發(fā)現(xiàn)了一些基因可以調(diào)控正在形成的重要通路。
科研人員還對HPRT基因做了直接的試驗(yàn)證實(shí),，通過對萊施-尼漢疾?。↙esch Nyhan disease）嚴(yán)重神經(jīng)紊亂的形成研究,，表明HPRT基因確實(shí)可能導(dǎo)致神經(jīng)學(xué)上的問題,。而這些問題會直接影響出生和神經(jīng)元的功能,，尤其是對多巴胺依賴的神經(jīng)傳導(dǎo)神經(jīng)元,。(生物谷Bioon.com)
生物谷推薦原始出處：
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.
