Essential role of the CUL4B ubiquitin ligase in extra-embryonic tissue development during mouse embryogenesis  

作　　者：Liren Liu Yan Yin Yuewei Li Lisa Prevedel Elizabeth H Lacy Liang Ma Pengbo Zhou 

机构地区：[1]Department of Pathology and Laborato~ Medicine, Weill Cornell Medical College and Weill Graduate School of Medical Sci-ences of Cornell University, New York, NY 10065, USA [2]Division of Dermatology, Washington University School of Medicine, St.Louis, MO 6311 O, USA [3]Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA

出　　处：《Cell Research》2012年第8期1258-1269,共12页细胞研究（英文版）

摘　　要：Mutations of the CUL4B ubiquitin ligase gene are causally linked to syndromic X-linked mental retardation （XLMR）. However, the pathogenic role of CUL4B mutations in neuronal and developmental defects is not understood. We have generated mice with targeted disruption of Cul4b, and observed embryonic lethality with pronounced growth inhibition and increased apoptosis in extra-embryonic tissues. Cul4b, but not its paralog Cul4a, is expressed at high levels in extra-embryonic tissues post implantation. Silencing of CUL4B expression in an extra-embryonic cell line resulted in the robust accumulation of the CUL4 substrate p21^Cipl/WAF and G2/M cell cycle arrest, which could be partially rescued by silencing of p21^Cipl/WAF. Epiblast-specific deletion of Cul4b prevented embryonic lethality and gave rise to viable Cul4b null mice. Therefore, while dispensable in the embryo proper, Cul4b performs an essential developmental role in the extra-embryonic tissues. Our study offers a strategy to generate viable Cul4b-deficient mice to model the potential neuronal and behavioral deficiencies of human CUL4B XLMR patients.

关 键 词：cullin 4B KNOCKOUT extra-embryonic tissue ubiquitin X-INACTIVATION 

分 类 号：Q939.4[生物学—微生物学] Q954.4