Abstract
Abstract: :
Purpose: High specificity for skin appendage formation is based on ectodysplasin (EDA), the protein encoded by the X–linked EDA gene. It intervenes in skin appendage development as a TNF family ligand, activating NF–kB and JNK– promoted transcription. Mutations in EDA genes result in X–linked ectodermal dysplasia syndrome in the human and the Tabby mouse (EDA negative). The purpose of this study is to describe the ocular abnormalities of Tabby and EDA transgenic mice. Methods: Linearized mEDA–A1 cDNA with tetracycline controllable promoter was injected into C57BL eggs and potential founders were mated to heterozygous Tabby females. The transgene carrying Tabby females were then mated to Tet–off male mice to activate transgene. Genetic background of transgenic mice was detected by SSCP. The eyes of Tabby (3), EDA Tg (4) and wild type (4), transgenic male mice ranging from 3 to 6 months of age were examined clinically under a dissecting microscope. After sacrificing the mice, one eye with intact eyelids and conjunctiva was fixed in 20% formalin, embedded in methacrylate and stained with hematoxylin and eosin; the fellow eye was embedded in OCT and prepared for frozen section. Results: Mutant Tabby mice lack sweat glands and 2 of the 3 types of back skin hair follicles. EDA Tg mice show repression of undercoat hair follicle formation in back skin and notably hyperplastic sebaceous glands in associated hair follicles. 3/3 Tabby mice demonstrated thickened, irregular lid margins, with loss of hair on the eyelids. In addition, the corneal surface was irregular and abundant mucus was present. 2/3 demonstrated corneal opacities. 1/3 EDA Tg mice showed decreased hair on eyelid margins and mild thickening (17 weeks). The wild type mice showed no significant abnormalities. Histology confirmed the absence of Meibomian glands in Tabby mice, and noted additional phenotypes, including ocular surface inflammation: blepharitis, conjunctivitis and keratitis, corneal neovascularization, and early keratinization. 3/4 WT mice showed no inflammation; 1 had minimal conjunctival inflammation. The EDA Tg mice appeared normal except for prominent sebaceous glands associated with hair follicles, 1 also had minimal conjunctivitis. Conclusions: Tabby mice demonstrate absent Meibomian glands as well as blepharitis, corneal and conjunctival inflammation and neovascularization, making them a useful model for ocular surface disease. EDA may play a role in ocular surface health via an impact on meibomian gland development and modulation of ocular surface inflammation.
Keywords: inflammation • eyelid • cornea: basic science