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G. D. Lively, A. Hedberg-Buenz, K. Wang, M. H. Kuehn, M. G. Anderson; Identification of a Locus Contributing to Murine Central Corneal Thickness. Invest. Ophthalmol. Vis. Sci. 2009;50(13):879.
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On average, African Americans have a central corneal thickness (CCT) 30 microns less than Caucasians. More than a mere anatomical curiosity, differences in CCT contribute to an important health disparity issue. CCT is an independent risk factor for glaucoma. Here, we initiate genetic studies to analyze the basic biology of CCT with a quantitative trait association approach utilizing inbred strains of mice.
Murine CCT was measured with an ultrasound pachymeter and reliability tested by comparing pachymetry measurements to measurements from unfixed cryosections. A strain survey was performed with 17 different inbred strains of mice. Corneas from three strains with non-overlapping differences in CCT (C57BLKS/J, C57BL/6J, and SJL/J) were compared by histology, TEM, and expression profiling with gene microarrays. The thinnest (C57BLKS/J) and thickest (SJL/J) strains were intercrossed, producing 225 F2 mice. These mice were phenotyped, the 20% extremes were genotyped, and associations were detected using interval-mapping to assign probabilities.
Reliability of the pachymeter was confirmed by comparing pachymetry and unfixed cryosection measurements (P>0.05, Wilcoxon signed-rank test). The strain survey identified several strains with statistically different CCT values (n = 8-10 eyes per strain; 100-120 days; P<0.05, Student’s t-test for all significantly different strains), and varied from 88.6 +/- 6.6 microns (mean +/- SD) in C57BLKS/J to 123.5 +/- 7.8 microns in SJL/J. Stromal and epithelial thicknesses were both found to be major determinants contributing to differing CCT in mice. Among multiple loci implicated in influencing murine CCT, a significant locus, Cctq1, was identified on chromosome 7 (max LOD score = 4.0, max heritability = 34%).
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