title: Targeted mutation of the murine goosecoid gene results in craniofacial defects and neonatal death.
abstract: The goosecoid gene encodes a homeodomain-containing protein that has been identified in a number of species and has been implicated in a variety of key developmental processes. Initially suggested to be involved in organizing the embryo during early development, goosecoid has since been demonstrated to be expressed during organogenesis-most notably in the head, the limbs and the ventrolateral body wall. To investigate the role of goosecoid in embryonic development, we have inactivated the gene by gene targeting to generate mice mutant for the goosecoid gene. Mice that are homozygous for the goosecoid mutation do not display a gastrulation phenotype and are born; however, they do not survive more than 24 hours. Analysis of the homozygotes revealed numerous developmental defects affecting those structures in which goosecoid is expressed during its second (late) phase of embryonic expression. Predominantly, these defects involve the lower mandible and its associated musculature including the tongue, the nasal cavity and the nasal pits, as well as the components of the inner ear (malleus, tympanic ring) and the external auditory meatus. Although the observed phenotype is in accordance with the late expression domains of goosecoid in wild-type embryos, we suggest that the lack of an earlier phenotype is the result of functional compensation by other genes.
authors.affiliation: Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Yamada
authors.forename: A
authors.initials: A
authors.lastname: Mansouri
authors.forename: M
authors.initials: M
authors.lastname: Torres
authors.forename: E T
authors.initials: ET
authors.lastname: Stuart
authors.forename: M
authors.initials: M
authors.lastname: Blum
authors.forename: M
authors.initials: M
authors.lastname: Schultz
authors.forename: E M
authors.initials: EM
authors.lastname: De Robertis
authors.forename: P
authors.initials: P
authors.lastname: Gruss
mesh_terms: D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D004268:DNA-Binding Proteins / Q000235:genetics*; D004423:Ear / Q000002:abnormalities; D005091:Exons; D005147:Facial Bones / Q000002:abnormalities*; D005313:Fetal Death / Q000235:genetics; D005775:Gastrula / Q000502:physiology*; D015870:Gene Expression; D018390:Gene Targeting; D005801:Genes, Homeobox; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D010641:Phenotype; D012097:Repressor Proteins; D012886:Skull / Q000002:abnormalities*; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D051956:Goosecoid Protein; C497993:Gsc protein, mouse; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D014157:Transcription Factors