| RRC ID |
2279
|
| Author |
Sakaki-Yumoto M, Kobayashi C, Sato A, Fujimura S, Matsumoto Y, Takasato M, Kodama T, Aburatani H, Asashima M, Yoshida N, Nishinakamura R.
|
| Title |
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.
|
| Journal |
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.
|
| Volume |
133(15)
|
| Pages |
3005-13
|
| Published |
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
|
| Times Cited |
185
|
|
WOS Category
|
DEVELOPMENTAL BIOLOGY
|
| Resource |
| DNA material |
AxCANCre (RDB01748) |
