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The novel Col8a2G257D mutant mouse line Aca23 – a model for endothelial corneal dystrophies
Author(s) -
PUK O,
AHMAD N,
GRAW J
Publication year - 2008
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2008.6351.x
Subject(s) - biology , mutant , cornea , genetics , corneal dystrophy , corneal endothelium , candidate gene , point mutation , descemet's membrane , gene , microbiology and biotechnology , endothelium , neuroscience
Purpose The purpose of this study was the morphological and genetic characterization of the novel eye‐size mutant Aca23 in the mouse. Methods The eyes of the mutants were described by histology and in situ hybridization. Visual properties were examined in the optokinetic drum. Linkage analysis was performed using single nucleotide polymorphisms and micro‐satellite markers. The Aca23 mutation was identified by sequence analysis of positional candidate genes. Results Aca23 (ACMaster abnormality) is a new dominant eye size mutant, which was recovered in an ENU mutagenesis program at the HMGU. The pathologic phenotype includes increased anterior chamber depths, longer axes, and reduced corneal thicknesses. Visual properties are not affected by these irregular eye size parameters. In genome wide mapping studies, Aca23 was linked to the distal part of chromosome 4 between the markers D4Mit249 and D4Mit73. A G→A point mutation was identified at cDNA position 770 of the candidate gene Col8a2, which belongs to the collagen superfamily. The transition results in a G257D amino acid exchange within the collagen triple helix repeat. Col8a2 is expressed in the posterior part of the cornea. These data suggest that effects on structure and elasticity of the corneal Descemet’s membrane might cause the corneal thinning and anterior expansion in Aca23 eyes. Comparable pathologic abnormalities can be observed in human Fuchs’ endothelial dystrophy of the cornea (FECD) and posterior polymorphous corneal dystrophy (PPCD). Conclusion The mouse mutant described here offers a novel mutated allele of the collagen type VIII gene Col8a2 and represents a new model for endothelial corneal dystrophies.