RRC ID 2279
著者 Sakaki-Yumoto M, Kobayashi C, Sato A, Fujimura S, Matsumoto Y, Takasato M, Kodama T, Aburatani H, Asashima M, Yoshida N, Nishinakamura R.
タイトル The murine homolog of SALL4, a causative gene in Okihiro syndrome, is essential for embryonic stem cell proliferation, and cooperates with Sall1 in anorectal, heart, brain and kidney development.
ジャーナル Development
Abstract 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.
巻・号 133(15)
ページ 3005-13
公開日 2006-8-1
DOI 10.1242/dev.02457
PII dev.02457
PMID 16790473
MeSH Animals Blastocyst / cytology Brain / embryology Cell Culture Techniques Cell Differentiation Crosses, Genetic DNA-Binding Proteins / genetics* Duane Retraction Syndrome / genetics* Genetic Carrier Screening Genotype Heart / embryology Kidney / embryology Mice RNA, Small Interfering / genetics Rectum / embryology Stem Cells / cytology* Transcription Factors / genetics* Transfection
IF 5.611
引用数 185
WOS 分野 DEVELOPMENTAL BIOLOGY
リソース情報
遺伝子材料 AxCANCre (RDB01748)