Kim J K, Huh S O, Choi H, Lee K S, Shin D, Lee C, Nam J S, Kim H, Chung H, Lee H W, Park S D, Seong R H
School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Kwanak-gu, Shinlim-dong, Seoul 151-742, Republic of Korea.
Mol Cell Biol. 2001 Nov;21(22):7787-95. doi: 10.1128/MCB.21.22.7787-7795.2001.
Srg3 (SWI3-related gene product) is a mouse homolog of yeast SWI3, Drosophila melanogaster MOIRA (also named MOR/BAP155), and human BAF155 and is known as a core subunit of SWI/SNF complex. This complex is involved in the chromatin remodeling required for the regulation of transcriptional processes associated with development, cellular differentiation, and proliferation. We generated mice with a null mutation in the Srg3 locus to examine its function in vivo. Homozygous mutants develop in the early implantation stage but undergo rapid degeneration thereafter. An in vitro outgrowth study revealed that mutant blastocysts hatch, adhere, and form a layer of trophoblast giant cells, but the inner cell mass degenerates after prolonged culture. Interestingly, about 20% of heterozygous mutant embryos display defects in brain development with abnormal organization of the brain, a condition known as exencephaly. Histological examination suggests that exencephaly is caused by the failure in neural fold elevation, resulting in severe brain malformation. Our findings demonstrate that Srg3 is essential for early embryogenesis and plays an important role in the brain development of mice.
Srg3(与SWI3相关的基因产物)是酵母SWI3、果蝇黑腹果蝇MOIRA(也称为MOR/BAP155)和人类BAF155的小鼠同源物,是SWI/SNF复合物的核心亚基。该复合物参与与发育、细胞分化和增殖相关的转录过程调控所需的染色质重塑。我们构建了Srg3基因座存在无效突变的小鼠,以研究其在体内的功能。纯合突变体在植入早期发育,但此后迅速退化。体外生长研究表明,突变胚泡孵化、粘附并形成一层滋养层巨细胞,但在长时间培养后内细胞团退化。有趣的是,约20%的杂合突变胚胎在脑发育中表现出缺陷,脑部组织异常,这种情况称为无脑畸形。组织学检查表明,无脑畸形是由神经褶隆起失败引起的,导致严重的脑畸形。我们的研究结果表明,Srg3对早期胚胎发育至关重要,在小鼠脑发育中起重要作用。