CUL4B是cullin-RING泛素連接酶家族的一員,,定位于X染色體上,。X染色體連鎖的智力障礙(XLMR)患者,常常伴有該基因的突變,。CUL4B缺陷患者常表現(xiàn)為青春期滯后,,身材矮小,性腺發(fā)育不良,,巨頭等一系列綜合征,。但CUL4B基因的具體功能卻一直都是個謎。
5月15日,,國際著名雜志Cell Research在線發(fā)表了Yongchao Zhao 和Yi Sun的研究論文“CUL4B ubiquitin ligase in mouse development: A model for human X-linked mental retardation syndrome,?”
研究者利用Cre-loxP系統(tǒng)構(gòu)建了CUL4B條件性敲除小鼠。他們發(fā)現(xiàn),,CUL4B可通過影響來源于卵黃囊的血液供應(yīng)及胚胎細(xì)胞的細(xì)胞周期調(diào)控來調(diào)節(jié)小鼠的發(fā)育,。該研究表明,CUL4B基因雖然在小鼠胚胎本身的發(fā)育中可有可無,,但卻在胚胎額外組織的發(fā)育中發(fā)揮重要的作用,。可存活的CUL4B基因敲除小鼠首次為研究X染色體連鎖的智力障礙(XLMR)患者的神經(jīng)和行為缺陷提供了動物模型,。(生物谷Bioon.com)
doi:10.1038/cr.2012.79
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CUL4B ubiquitin ligase in mouse development:A model for human X-linked mental retardation syndrome,?
Yongchao Zhao1 and Yi Sun1
1Division of Radiation and Cancer Biology, Department of Radiation Oncology,, University of Michigan,, 4424B MS-1, 1301 Catherine Street,, Ann Arbor,, MI 48109, USA
Correspondence:Yi Sun,,Tel: 734-615-1989,;Fax:734-763-1581
CUL4B, a member of the cullin-RING ubiquitin ligase family,, is frequently mutated in X-linked mental retardation (XLMR) patients. The study by Liu et al. showed that Cul4b plays an essential developmental role in the extra-embryonic tissues,, while it is dispensable in the embryo proper during mouse embryogenesis. Viable Cul4b-null mice provide the first animal model to study neuronal and behavioral deficiencies seen in human CUL4B XLMR patients.