Quantitative trait loci associated with murine central corneal thickness

Abstract

The cornea is a specialized transparent tissue responsible for refracting light, serving as a protective barrier, and lending structural support to eye shape. Given its importance, the cornea exhibits a surprising amount of phenotypic variability in some traits, including central corneal thickness (CCT). More than a mere anatomic curiosity, differences in CCT have recently been associated with risk for glaucoma. Although multiple lines of evidence support a strong role for heredity in regulating CCT, the responsible genes remain unknown. To better understand the genetic basis of CCT variability, we conducted a genomewide quantitative trait locus (QTL) analysis with (C57BLKS/J x SJL/J) F(2) mice. This experiment identified a locus, Cctq1 (central corneal thickness QTL 1) on chromosome 7 (Chr 7; peak, 105 Mb), that is significantly associated with CCT. To independently test the biological significance of these results, (C57BLKS/J x NZB/B1NJ) F(2) mice were generated and analyzed for associations with Chr 7. This experiment identified a significant association at 131 Mb. Furthermore, low-generation congenic mice in which the Chr 7 QTL interval from the SJL strain was transferred onto the KS background had CCT values significantly higher than inbred KS mice. These results demonstrate that the genetic dependence of CCT in mice is a multigenic trait, which in these contexts is significantly regulated by a region on Chr 7. Future identification of the genes for these QTL will provide improved understanding of the processes regulating CCT and the pathophysiology of glaucoma.