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Viable EdnraY129F mice feature human mandibulofacial dysostosis with alopecia (MFDA) syndrome due to the homologue mutation.

Mamm. Genome 27, 587-598 (2016)
Publishers Version Research data DOI PMC
Open Access Gold (Paid Option)
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as soon as is submitted to ZB.
Animal models resembling human mutations are valuable tools to research the features of complex human craniofacial syndromes. This is the first report on a viable dominant mouse model carrying a non-synonymous sequence variation within the endothelin receptor type A gene (Ednra c.386A>T, p.Tyr129Phe) derived by an ENU mutagenesis program. The identical amino acid substitution was reported recently as disease causing in three individuals with the mandibulofacial dysostosis with alopecia (MFDA, OMIM 616367) syndrome. We performed standardized phenotyping of wild-type, heterozygous, and homozygous Ednra (Y129F) mice within the German Mouse Clinic. Mutant mice mimic the craniofacial phenotypes of jaw dysplasia, micrognathia, dysplastic temporomandibular joints, auricular dysmorphism, and missing of the squamosal zygomatic process as described for MFDA-affected individuals. As observed in MFDA-affected individuals, mutant Ednra (Y129F) mice exhibit hearing impairment in line with strong abnormalities of the ossicles and further, reduction of some lung volumetric parameters. In general, heterozygous and homozygous mice demonstrated inter-individual diversity of expression of the craniofacial phenotypes as observed in MFDA patients but without showing any cleft palates, eyelid defects, or alopecia. Mutant Ednra (Y129F) mice represent a valuable viable model for complex human syndromes of the first and second pharyngeal arches and for further studies and analysis of impaired endothelin 1 (EDN1)-endothelin receptor type A (EDNRA) signaling. Above all, Ednra (Y129F) mice model the recently published human MFDA syndrome and may be helpful for further disease understanding and development of therapeutic interventions.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Pharyngeal Arch Development; Endothelin Receptor-type; Airway Smooth-muscle; A Receptor; Enu Mutagenesis; Deficient Mice; Bone-formation; Cleft-palate; Mouse Model; Insights
Reviewing status