{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:58:06Z","timestamp":1791197886426,"version":"4.1.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Dev Biol"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The H6 homeobox genes <jats:italic>Hmx1<\/jats:italic>, <jats:italic>Hmx2<\/jats:italic>, and <jats:italic>Hmx3<\/jats:italic> (also known as <jats:italic>Nkx5-3<\/jats:italic>; <jats:italic>Nkx5-2<\/jats:italic> and <jats:italic>Nkx5-1<\/jats:italic>, respectively), compose a family within the NKL subclass of the ANTP class of homeobox genes. Hmx gene family expression is mostly limited to sensory organs, branchial (pharyngeal) arches, and the rostral part of the central nervous system. Targeted mutation of either <jats:italic>Hmx2<\/jats:italic> or <jats:italic>Hmx3<\/jats:italic> in mice disrupts the vestibular system. These tandemly duplicated genes have functional overlap as indicated by the loss of the entire vestibular system in double mutants. Mutants have not been described for <jats:italic>Hmx1<\/jats:italic>, the most divergent of the family.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Dumbo (<jats:italic>dmbo<\/jats:italic>) 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 <jats:italic>Hmx1<\/jats:italic>. 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 <jats:italic>dmbo\/dmbo<\/jats:italic> 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 <jats:italic>dumbo<\/jats:italic> 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 (<jats:italic>Hmx1<\/jats:italic>; also <jats:italic>Nkx5-3<\/jats:italic>). An independent spontaneous allele called misplaced ears (<jats:italic>mpe<\/jats:italic>) was also identified, confirming <jats:italic>Hmx1<\/jats:italic> as the responsible mutant gene.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The divergence of <jats:italic>Hmx1<\/jats:italic> from its paralogs is reflected by different and diverse developmental roles exclusive of vestibular involvement. Additionally, these mutant <jats:italic>Hmx1<\/jats:italic> alleles represent the first mouse models of a recently-discovered Oculo-Auricular syndrome caused by mutation of the orthologous human gene.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-213x-9-27","type":"journal-article","created":{"date-parts":[[2009,4,21]],"date-time":"2009-04-21T06:16:23Z","timestamp":1240294583000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Mouse H6 Homeobox 1 (Hmx1) mutations cause cranial abnormalities and reduced body mass"],"prefix":"10.1186","volume":"9","author":[{"given":"Robert J","family":"Munroe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinay","family":"Prabhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg M","family":"Acland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth R","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda S","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim P","family":"O'Brien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian C","family":"Welsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drew M","family":"Noden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C","family":"Schimenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2009,4,20]]},"reference":[{"key":"431_CR1","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/1741-7007-5-47","volume":"5","author":"PW Holland","year":"2007","unstructured":"Holland PW, Booth HA, Bruford EA: Classification and nomenclature of all human homeobox genes. 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