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Validity of the Hfm transgenic mouse as a model for hemifacial microsomia
Richard Cousley1, Hiroyuki Naora, Minesuke Yokoyama
1Orthodontic Department, Leeds Dental Institute, Leeds, England. rcousley@yahoo.com
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.
Insights
A genetic mutation in the Hfm mouse model reveals insights into hemifacial microsomia (HFM) causation. This study validates the Hfm mouse as a model for HFM-microtia spectrum, suggesting genetic factors contribute to these craniofacial anomalies.
Area of Science:
- Developmental Biology
- Genetics
- Craniofacial Biology
Background:
- Hemifacial microsomia (HFM) presents a diverse phenotype with unclear origins, traditionally attributed to embryonic hemorrhages.
- A transgenic Hfm mutation offers a potential genetic model for understanding HFM etiology.
Purpose of the Study:
- To investigate the validity of the Hfm transgenic mouse model for hemifacial microsomia.
- To examine the craniofacial phenotype and embryonic head development in Hfm mice.
Main Methods:
- Analysis of Hfm craniofacial phenotype in transgenic mice.
- Histological examination of embryonic head development (E13.5-17.5).
- Assessment of mutation transmission, penetrance, and viability.
Main Results:
- Loss-of-function Hfm mutation is autosomal dominant with reduced penetrance; only heterozygotes are viable.
- Extended Hfm phenotype includes anomalies of the ear, jaw, cranial base, maxilla, pharynx, TMJ, and palate.
- Novel finding of inner ear transposition in some Hfm embryos.
Conclusions:
- The Hfm transgenic mouse is a valuable model for the HFM-microtia spectrum.
- Findings support a genetic basis for HFM, potentially involving mesenchymal disruptions and embryonic hemorrhages.