%0 Journal Article
%T Mouse H6 Homeobox 1 (Hmx1) mutations cause cranial abnormalities and reduced body mass
%A Robert J Munroe
%A Vinay Prabhu
%A Greg M Acland
%A Kenneth R Johnson
%A Belinda S Harris
%A Tim P O'Brien
%A Ian C Welsh
%A Drew M Noden
%A John C Schimenti
%J BMC Developmental Biology
%D 2009
%I BioMed Central
%R 10.1186/1471-213x-9-27
%X Dumbo (dmbo) is a semi-lethal mouse mutation that was recovered in a forward genetic mutagenesis screen. Mutants exhibit enlarged ear pinnae with a distinctive ventrolateral shift. Here, we report on the basis of this phenotype and other abnormalities in the mutant, and identify the causative mutation as being an allele of Hmx1. Examination of dumbo skulls revealed only subtle changes in cranial bone morphology, namely hyperplasia of the gonial bone and irregularities along the caudal border of the squamous temporal bone. Other nearby otic structures were unaffected. The semilethality of dmbo/dmbo mice was found to be ~40%, occured perinatally, and was associated with exencephaly. Surviving mutants of both sexes exhibited reduced body mass from ~3 days postpartum onwards. Most dumbo adults were microphthalmic. Recombinant animals and specific deletion-bearing mice were used to map the dumbo mutation to a 1.8 Mb region on Chromosome 5. DNA sequencing of genes in this region revealed a nonsense mutation in the first exon of H6 Homeobox 1 (Hmx1; also Nkx5-3). An independent spontaneous allele called misplaced ears (mpe) was also identified, confirming Hmx1 as the responsible mutant gene.The divergence of Hmx1 from its paralogs is reflected by different and diverse developmental roles exclusive of vestibular involvement. Additionally, these mutant Hmx1 alleles represent the first mouse models of a recently-discovered Oculo-Auricular syndrome caused by mutation of the orthologous human gene.Homeobox proteins, characterized by the presence of a conserved 60 amino acid homeodomain, are encoded by a large group of genes that have diverse functions in development. Humans have about 235 functional homeobox genes that have been categorized into 11 major classes representing 102 families [1]. The ANTP (Antennapedia) class contains the highly studied HOX-like (HOXL) subclass of genes that are best known for their roles in specifying body plan organization from flies to mammals.
%U http://www.biomedcentral.com/1471-213X/9/27