X-linked anhidrotic ectodermal dysplasia disruption yields a mouse model for ocular surface disease and resultant blindness.
X-linked anhidrotic/hypohidrotic ectodermal dysplasia (EDA) is caused by mutations in the (EDA) gene, which is required for the morphogenesis of ectoderm-derived tissues. Although EDA function in skin appendage development has been studied in Eda mutant "Tabby" mice, we have recently identified characteristic abnormalities in the ocular surface, an ectoderm-derived tissue. Histology of eyes of Tabby males revealed that 1) as previously reported, mice lacked meibomian glands; 2) >80% developed corneal lesions such as neovascularization, keratitis, ulceration, and keratinization identifiable from 9 weeks of age; and 3) > 80% showed ocular surface inflammation (blepharitis and conjunctivitis) when housed in a standard environment. Strikingly, both corneal defects and inflammation were prevented in Tabby mice bearing a transgene for the Eda-A1 isoform, but meibomian glands were restored little if at all. These findings suggest that intact ocular surface health is EDA dependent and that Tabby corneal abnormalities are not solely dependent on meibomian gland lipid secretion. Alternatively, susceptibility to inflammation and other phenotypes could result from failure of the usual EDA receptor to activate nuclear factor-kappaB transcription factors. This can be further tested in Tabby and Tabby-EDA transgenic mice, which provide unique models of severe ocular surface disease.
Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Chang-Yi
CY
Cui
Janine A
JA
Smith
David
D
Schlessinger
Chi-Chao
CC
Chan
D000818:Animals; D001766:Blindness / Q000235:genetics; D003316:Corneal Diseases / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000473:pathology; D053331:Ectodysplasins; D005141:Eyelid Diseases / Q000235:genetics* / Q000473:pathology; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000473:pathology; D008297:Male; D008537:Meibomian Glands / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics; D019076:Transgenes
D053331:Ectodysplasins; C506019:Eda protein, mouse; D008565:Membrane Proteins; D020033:Protein Isoforms