title: A Sall4 mutant mouse model useful for studying the role of Sall4 in early embryonic development and organogenesis.
abstract: SALL4 is a homologue of the Drosophila homeotic gene spalt, a zinc finger transcription factor, required for inner cell mass proliferation in early embryonic development. It also interacts with other transcription factors to control the development of the anorectal region, kidney, heart, limbs, and brain. Truncating mutations in SALL4 cause Okihiro syndrome, manifest as Duane anomaly, radial ray defects and sensorineural and conductive deafness. We report the characterization of a novel murine Sall4 null allele created by bacterial recombineering in ES cells. Homozygous mutant mice exhibit early embryonic lethality. Heterozygous mutant mice recapitulate phenotypic features of Okihiro syndrome including deafness, lower anogenital tract abnormalities, renal hypoplasia, anencephaly, Hirschprung's disease, and skeletal defects. This phenotype shows important differences in cardiac and ear manifestations to previously characterized Sall4 mutant alleles and should prove useful for the investigation of the influence of modifier alleles and protein interactions on the transcriptional regulatory function of Sall4.
authors.forename: Madhuri
authors.initials: M
authors.lastname: Warren
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Sarah
authors.initials: S
authors.lastname: Spiden
authors.forename: Dongrong
authors.initials: D
authors.lastname: Chen-Murchie
authors.forename: David
authors.initials: D
authors.lastname: Tannahill
authors.forename: Karen P
authors.initials: KP
authors.lastname: Steel
authors.forename: Allan
authors.initials: A
authors.lastname: Bradley
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004370:Duane Retraction Syndrome / Q000196:embryology / Q000235:genetics; D047108:Embryonic Development; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009154:Mutation; D038081:Organogenesis; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; C509167:Sall4 protein, mouse; D014157:Transcription Factors