title: Chondrodystrophic mice with coincidental agnathia: evidence for the tongue obstruction hypothesis in cleft palate.
abstract: Mice homozygous for either of two mutations, chondrodysplasia (cho) or cartilage matrix deficiency (cmd), have short-limbed chondrodystrophy. This phenotype includes retrognathia, relative macroglossia, and cleft palate. It has been postulated that the cleft palate in these mice is the result of tongue obstruction during palatogenesis. Agnathia associated with microglossia is an independent spontaneously occurring defect in the strains bearing these mutations. The coincidental occurrence of agnathia-microglossia with chondrodystrophy lends itself to the study of the mechanism of cleft palate formation. We examined approximate midsagittal histological sections of normal and chondrodystrophic newborn mice, both with and without agnathia. Mandibular measurements and examinations of palate closure and tongue structure were made from photographic prints. Typical chondrodystrophic mutants with cleft palates had a mean mandibular length that was 66% of normal and a tongue that appeared large relative to the shortened mandible. Chondrodystrophic mutants with agnathia and microglossia had a mean mandibular length that was further reduced to 30% of normal, yet had a closed palate. We also observed two nonagnathic chondrodystrophic mutants that had slightly decreased mandibular lengths, microglossia, and closed palates. These observations suggest that tongue obstruction during palatogenesis is the pathogenetic mechanism of cleft palate in chondrodystrophic mice. A similar tongue obstruction hypothesis has been proposed as the mechanism of cleft palate formation in the human Pierre Robin sequence, which consists of retrognathia, glossoptosis, and cleft palate. This mechanistic hypothesis has been challenged, but our findings support the tongue obstruction hypothesis in the Robin cleft.
authors.affiliation: Department of Zoology, Brigham Young University, Provo, Utah 84602.
authors.forename: L
authors.initials: L
authors.lastname: Clarke
authors.forename: W B
authors.initials: WB
authors.lastname: Hepworth
authors.forename: J C
authors.initials: JC
authors.lastname: Carey
authors.forename: R E
authors.initials: RE
authors.lastname: Seegmiller
mesh_terms: D000015:Abnormalities, Multiple; D000818:Animals; D002972:Cleft Palate / Q000209:etiology*; D005097:Exostoses, Multiple Hereditary / Q000150:complications* / Q000473:pathology; D008334:Mandible / Q000002:abnormalities*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010641:Phenotype; D014059:Tongue / Q000002:abnormalities* / Q000473:pathology