title: Validity of the Hfm transgenic mouse as a model for hemifacial microsomia.
abstract: OBJECTIVE
  Our comprehension of hemifacial microsomia (HFM) has been hindered by its diverse phenotype and unclear etiopathogenesis. The conventional view has been that HFM's facial defects result from embryonic hemorrhages in the region of the first and second branchial arches. A more recent model based on a transgenic mutation of a locus termed Hfm (B1 to B3 on chromosome 10) appears to provide an insight into HFM causation. This study investigated the validity of this model by examining the Hfm craniofacial phenotype and histological development of the embryonic head (E13.5 to 17.5).
  
  
  RESULTS
  The results confirmed that although the loss-of-function mutation was transmitted in an autosomal dominant manner, the penetrance rate was significantly reduced and only Hfm heterozygotes were viable. The observations here extend the Hfm phenotype beyond microtia and jaw asymmetry to include structural and positional anomalies affecting the external auditory meatus, middle ear, cranial base, maxilla, and pharyngeal structures. Temporomandibular joint (TMJ) development and palatal shelf fusion were also affected in a small number of cases. In addition, some Hfm embryos displayed a novel finding: transposition of the developing inner ear between the tubotympanic recess and cranial base.
  
  
  CONCLUSIONS
  These craniofacial features, especially the ear anomalies and facial asymmetry indicate that the Hfm transgenic mouse represents a useful model for the HFM-microtia spectrum. In particular, it supports the hypothesis that at least a proportion of HFM anomalies has a genetic causation mediated via mesenchymal disruptions and possibly embryonic hemorrhages.
authors.affiliation: Orthodontic Department, Leeds Dental Institute, Leeds, England. rcousley@yahoo.com
authors.forename: Richard
authors.initials: R
authors.lastname: Cousley
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Naora
authors.forename: Minesuke
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Minoru
authors.initials: M
authors.lastname: Kimura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Otani
mesh_terms: D000818:Animals; D001934:Branchial Region / Q000196:embryology; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D004195:Disease Models, Animal; D004424:Ear Canal / Q000002:abnormalities; D004431:Ear, External / Q000002:abnormalities; D007758:Ear, Inner / Q000002:abnormalities; D004432:Ear, Middle / Q000002:abnormalities; D005146:Facial Asymmetry / Q000196:embryology / Q000235:genetics*; D005799:Genes, Dominant / Q000235:genetics; D005838:Genotype; D006470:Hemorrhage / Q000196:embryology; D006579:Heterozygote; D006801:Humans; D008334:Mandible / Q000002:abnormalities; D008437:Maxilla / Q000002:abnormalities; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010159:Palate / Q000002:abnormalities; D010614:Pharynx / Q000002:abnormalities; D010641:Phenotype; D015203:Reproducibility of Results; D019291:Skull Base / Q000002:abnormalities; D013704:Temporomandibular Joint / Q000002:abnormalities