Congenital Stromal Corneal Dystrophy is not reproduced in 952delT Dcn Transgenic Mice

Abstract

Purpose: Congenital Stromal Corneal Dystrophy (CSCD) is a dominantly inherited condition which causes clouding of the corneal stroma in humans due to a point mutation in the decrin gene. To replicate this condition in mice, a transgene mouse strain, 952delT Dcn knock-in mice was created using homologous recombination.

Methods: The transgene mouse strain was created using homologous recombination. DNA sequencing confirmed the correct genotype. Animal research was conducted in compliance with the “ARVO Statement of the Use of Animals in Ophthalmic and Visual Research”.

Results: Corneas were clear, and the pathognomonic electron-lucent deposits described in human disease by electron microscopy were not identified. Furthermore, organ examination by light microscopy did not reveal any pathologic conditions. DCN mRNA length was similar and mRNA from both wt and mutant alleles associated to a similar degree with active polysomes as determined by density gradient centrifugation. In addition, we were unable to detect increased degradation of mRNA or protein. However, while nearly equivalent amounts of normal and truncated decorin is present in human CSCD corneas, truncated decorin was hardly detectable in corneas from the transgenic mice. In primary cultures of mouse corneal explants, truncated decorin was retained intracellularly in contrast to human corneal explants where truncated decorin was exported into the tissue culture medium.

Conclusions: We hypothesize that in our transgenic mice the amount of truncated decorin present in the cornea is too low to produce the effect required to generate the corneal phenotype seen in humans with the 967delT DCN mutation.

Keywords: 539 genetics • 541 glycoconjugates/glycoproteins • 740 transgenics/knock-outs