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Molecular and Cellular Biology, November 2001, p. 7787-7795, Vol. 21, No. 22
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.22.7787-7795.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Srg3, a Mouse Homolog of Yeast SWI3, Is Essential for Early Embryogenesis and Involved in Brain Development

Joong K. Kim,1 Sung-Oh Huh,2 Heonsik Choi,1 Kee-Sook Lee,3 Dongho Shin,1 Changjin Lee,1 Ju-Suk Nam,2 Hyun Kim,4 Heekyoung Chung,1 Han W. Lee,5 Sang D. Park,1 and Rho H. Seong1,*

School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Kwanak-gu, Shinlim-dong, Seoul 151-742,1 Department of Pharmacology and Institute of Natural Medicine, College of Medicine, Hallym University, Chunchon 200-702,2 Hormone Research Center, Chonnam National University, Kwangju 500-757,3 Institute of Human Genetics and Department of Anatomy, College of Medicine, Korea University, Seoul 136-705,4 and School of Medicine, Sung Kyun Kwan University, Suwon 440-746,5 Republic of Korea

Received 21 June 2001/Returned for modification 3 August 2001/Accepted 15 August 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.

* Corresponding author. Mailing address: Institute of Molecular Biology and Genetics, Seoul National University, Kwanak-gu, Shinlim-dong, San 56-1 Bldg. 105, Seoul 151-742, Korea. Phone: 82-2-880-7567. Fax: 82-2-887-9984. E-mail: rhseong{at}plaza.snu.ac.kr.

Molecular and Cellular Biology, November 2001, p. 7787-7795, Vol. 21, No. 22
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.22.7787-7795.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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