Overlapping and unique roles for C-terminal binding protein 1 (CtBP1) and CtBP2 during mouse development.

Overlapping and unique roles for C-terminal binding protein 1 (CtBP1) and CtBP2 during mouse development.
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DOI:
10.1128/mcb.22.15.5296-5307.2002
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发表时间:
2002-08-01
影响因子:
5.3
通讯作者:
Soriano, P
Soriano, P
中科院分区:
生物学2区
文献类型:
--
作者:
Hildebrand, JD;Soriano, P

文献摘要

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c端结合蛋白(CtBP)家族蛋白通过与许多转录因子的关联与多种生物过程有关。我们培育了Ctbp1和Ctbp2突变的小鼠,以研究CtBPs在脊椎动物发育过程中的体内功能。Ctbp1突变小鼠体积小,但具有活力和可育性,而ctbp2缺失小鼠由于胚胎外发育异常而在E10.5时死亡。携带Ctbp1和Ctbp2突变等位基因的各种组合的小鼠在广泛的发育过程中表现出剂量敏感缺陷。强烈的遗传相互作用以及对ctbp缺陷细胞的转录分析表明,ctbp在调节基因表达方面具有重叠作用。我们认为,观察到的表型反映了大量转录因子的活性在缺乏CtBP的情况下受到损害。
The C-terminal binding protein (CtBP) family of proteins has been linked to multiple biological processes through their association with numerous transcription factors. We generated mice harboring mutations in both Ctbp1 and Ctbp2 to address the in vivo function of CtBPs during vertebrate development. Ctbp1 mutant mice are small but viable and fertile, whereas Ctbp2-null mice show defects in axial patterning and die by E10.5 due to aberrant extraembryonic development. Mice harboring various combinations of Ctbp1 and Ctbp2 mutant alleles exhibit dosage-sensitive defects in a wide range of developmental processes. The strong genetic interaction, as well as transcription assays with CtBP-deficient cells, indicates that CtBPs have overlapping roles in regulating gene expression. We suggest that the observed phenotypes reflect the large number of transcription factors whose activities are compromised in the absence of CtBP.