Abstract
Purpose :
To generate a cornea-specific plakoglobin (JUP; juntion plakoglobin) knockout mouse and examin its corneal structure as well as wound helaing in the mouse. JUP, a member of the armadillo family and homologous to β-catenin, is common component to both adherens junctions and desmosomes.
Methods :
JUP flox mice and keratin 12 (Krt12)-Cre recombinase tarnsgenic mice were used and we generated corneal epithelium-specific plakoglobin knockout mice Krt12Cre/Jupf/f (JupCEΔ/CEΔ, homozygous corneal epithelium deletion). To evaluate the intraepithelial differentiation from basal cells to superficial cells, histology and immunostaining for keratin 14 and BrdU incorporastion were performed. In vivo healing of epithelium debridement (2 mm in diameter) in the corneal epithelium was then evaluated at every 6 hrs until 48 hrs.
Results :
We successfully obtained two JupCEΔ/ΔCE mice out of 202 bitrangenic mice, in which Jup was deleted in corneal epithelium-specific, although both Krt12 and JUP locate in mouse chromosome 11 (0.55 cM distance). After expnading the colony, the JupCEΔ/ΔCE mice manifested abnormalities in corneal epithelium. Basal cell-like cells labeled for keratin 14 were present in the supra-basal layer in corneal epithelium of JupCEΔ/ΔCE mice, although loss of JUP did not affcet BrdU incorporation. Closure of the epithelial debridement was significantly delayed until 30 hrs of epithelium debridement.
Conclusions :
Plakoglobin is essential to the maintenance of the structure of the corneal epithelium and its successful wound healing.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.