Validity of the Hfm transgenic mouse as a model for hemifacial microsomia.
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.
Cousley
Richard
R
Orthodontic Department, Leeds Dental Institute, Leeds, England. rcousley@yahoo.com
Naora
Hiroyuki
H
Yokoyama
Minesuke
M
Kimura
Minoru
M
Otani
Hiroki
H
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