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.
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.
authors.affiliation: Division of Integrative Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Sakaki-Yumoto
authors.forename: Chiyoko
authors.initials: C
authors.lastname: Kobayashi
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.forename: Sayoko
authors.initials: S
authors.lastname: Fujimura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Takasato
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Makoto
authors.initials: M
authors.lastname: Asashima
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Yoshida
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishinakamura
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology; D001921:Brain / Q000196:embryology; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000235:genetics*; D004370:Duane Retraction Syndrome / Q000235:genetics*; D006580:Genetic Carrier Screening; D005838:Genotype; D006321:Heart / Q000196:embryology; D007668:Kidney / Q000196:embryology; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D012007:Rectum / Q000196:embryology; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; C491254:Sall1 protein, mouse; C509167:Sall4 protein, mouse; D014157:Transcription Factors