Kim Jieun, Kaartinen Vesa
Developmental Biology Program, The Saban Research Institute of Childrens Hospital Los Angeles, Department of Pathology, The Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Genesis. 2008 Jun;46(6):329-33. doi: 10.1002/dvg.20401.
Trim33 (Tif1gamma, ectodermin, moonshine), a member of the TIF1 family of transcriptional coactivators and corepressors, is a large nuclear protein that contains an N-terminal tripartite (Trim) domain composed of a RING domain, two B-box domains, and a coiled coil domain. It has been suggested that Trim33 (Ectodermin) mediates ectodermal induction in the Xenopus by functioning as a Smad4 ubiquitin ligase, while in the zebrafish Trim33 (moonshine) has been reported to act as a R-Smad binding protein in induction of erythroid differentiation. Since the developmental role of Trim33 in mammals is currently unknown, we generated mice carrying the conditional Trim33 (Trim33(FX)) allele by flanking exons 2-4 encoding most of the functionally critical N-terminal tripartite domain by loxP sites. We confirmed the null genotype by using the EIIa-Cre transgenic approach to create mice that lack exons 2-4. Embryos deficient in Trim33 die during early somitogenesis, demonstrating that Trim33 plays an important nonredundant role in mammalian embryonic development.
Trim33（Tif1γ、外胚层决定蛋白、月光蛋白）是转录共激活因子和共抑制因子TIF1家族的成员，是一种大型核蛋白，其N端包含一个由RING结构域、两个B-box结构域和一个卷曲螺旋结构域组成的三联体（Trim）结构域。有研究表明，Trim33（外胚层决定蛋白）在非洲爪蟾中作为Smad4泛素连接酶介导外胚层诱导，而在斑马鱼中，Trim33（月光蛋白）据报道在红细胞分化诱导中作为R-Smad结合蛋白发挥作用。由于Trim33在哺乳动物发育中的作用目前尚不清楚，我们通过在编码大部分功能关键的N端三联体结构域的外显子2-4两侧插入loxP位点，构建了携带条件性Trim33（Trim33(FX)）等位基因的小鼠。我们通过使用EIIa-Cre转基因方法创建缺失外显子2-4的小鼠，证实了无效基因型。Trim33缺陷的胚胎在早期体节形成过程中死亡，表明Trim33在哺乳动物胚胎发育中发挥重要的非冗余作用。
