期刊
DEVELOPMENT
卷 133, 期 15, 页码 3005-3013出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.02457
关键词
Sall4; spalt; embryonic stem cells; Okihiro syndrome; Townes-Brocks syndrome; organogenesis; mouse
Mutations in SALL4, the human homolog of the Drosophila homeotic gene spalt ( sal), cause the autosomal dominant disorder known as Okihiro syndrome. In this study, we show that a targeted null mutation in the mouse Sall4 gene leads to lethality during peri-implantation. Growth of the inner cell mass from the knockout blastocysts was reduced, and Sall4-null embryonic stem ( ES) cells proliferated poorly with no aberrant differentiation. Furthermore, we demonstrated that anorectal and heart anomalies in Okihiro syndrome are caused by Sall4 haploinsufficiency and that Sall4/Sall1 heterozygotes exhibited an increased incidence of anorectal and heart anomalies, exencephaly and kidney agenesis. Sall4 and Sall1 formed heterodimers, and a truncated Sall1 caused mislocalization of Sall4 in the heterochromatin; thus, some symptoms of Townes-Brocks syndrome caused by SALL1 truncations could result from SALL4 inhibition.
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