title: Identification and developmental expression analysis of a novel homeobox gene closely linked to the mouse Twirler mutation.
abstract: The Twirler mutation arose spontaneously and causes inner ear defects in heterozygous and cleft lip and/or cleft palate in homozygous mutant mice, providing a unique animal model for investigating the molecular mechanisms of inner ear and craniofacial development. Here, we report the identification of a novel homeobox gene, Iroquois-related homeobox like-1 (Irxl1), from the Twirler locus. Irxl1 encodes a TALE-family homeodomain protein with its homeodomain exhibiting the highest amino acid sequence identity (54%) to those of invertebrate Iroquois and vertebrate Irx subfamily members. The putative Irxl1 protein lacks the Iro-box, a conserved motif in all known members of the Irx subfamily. Searching the databases showed that Irxl1 orthologs exist in Xenopus, chick, and mammals. In situ hybridization analyses of mouse embryos at various developmental stages showed that Irxl1 mRNA is highly expressed in the frontonasal process and palatal mesenchyme during primary and secondary palate development. In addition, Irxl1 mRNA is strongly expressed in mesenchyme surrounding the developing inner ear, in discrete regions of the developing mandible, in the dermamyotome during somite differentiation, and in a subset of muscular structures in late embryonic stages. The developmental expression pattern indicates that Irxl1 is a good candidate gene for the Twirler gene.
authors.affiliation: Department of Biology, University of Rochester, Rochester, NY 14627, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Liu
authors.forename: Wenjin
authors.initials: W
authors.lastname: Liu
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Maltby
authors.forename: Yu
authors.initials: Y
authors.lastname: Lan
authors.forename: Rulang
authors.initials: R
authors.lastname: Jiang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002971:Cleft Lip / Q000235:genetics; D002972:Cleft Palate / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000302:isolation & purification; D007758:Ear, Inner / Q000196:embryology; D004622:Embryo, Mammalian / Q000378:metabolism; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D018076:DNA, Complementary; D018398:Homeodomain Proteins; D012097:Repressor Proteins; C490797:Tgif1 protein, mouse; C510657:mohawk protein, mouse