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Molecular and Cellular Biology, June 2005, p. 4683-4692, Vol. 25, No. 11
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.11.4683-4692.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Smad1 and Smad8 Function Similarly in Mammalian Central Nervous System Development

Department of Molecular Genetics and Division of Human Cancer Genetics, Ohio State University, 484 W. 12th Ave., Columbus, Ohio 43210,¹ Center for Molecular and Human Genetics, Columbus Children's Research Institute, and Department of Pediatrics, College of Medicine and Public Health, Ohio State University, Columbus, Ohio 43205²

Received 30 September 2004/ Returned for modification 2 December 2004/ Accepted 3 March 2005

Smads 1, 5, and 8 are the intracellular mediators for the bone morphogenetic proteins (BMPs), which play crucial roles during mammalian development. Previous research has shown that Smad1 is important in the formation of the allantois, while Smad5 has been shown to be critical in the process of angiogenesis. To further analyze the BMP-responsive Smads, we disrupted the murine Smad8 gene utilizing the Cre/loxP system. A Smad8 hypomorphic allele (Smad8^exon3) was constructed that contains an in-frame deletion of exon 3, removing one-third of the MH2 domain and a small portion of the linker region. Xenopus injection assays indicated that this Smad8 deletion allele is still functional but has reduced ventralizing capability compared to the wild type. Although Smad8^exon3/exon3 embryos are phenotypically normal, homozygotes of another hypomorphic allele of Smad8 (Smad8^3loxP) containing a neomycin cassette within intron 3, phenocopy an embryonic brain defect observed in roughly 22% of Smad1^+/– embryos analyzed at embryonic day 11.5. These observations suggest that BMP-responsive Smads have critical functions in the development of the mammalian central nervous system.

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