Genetic dependence of central corneal thickness among inbred strains of mice.
OBJECTIVE
Central corneal thickness (CCT) exhibits broad variability. For unknown reasons, CCT also associates with diseases not typically considered corneal, particularly glaucoma. The purpose of this study was to test the strain dependence of CCT variability among inbred mice and identify cellular and molecular factors associated with differing CCT.


METHODS
Methodology for measuring murine CCT with ultrasound pachymetry was developed and used to measure CCT among 17 strains of mice. Corneas from three strains with nonoverlapping differences in CCT (C57BLKS/J, C57BL/6J, and SJL/J) were compared by histology, transmission electron microscopy, and expression profiling with gene microarrays.


RESULTS
CCT in mice was highly strain dependent. CCT exhibited continuous variation from 89.2 microm in C57BLKS/J to 123.8 microm in SJL/J. Stromal thickness was the major determinant of the varying murine CCT, with epithelial thickness also contributing. Corneal expression levels of many genes differed between strains with differing CCT, but most of these changes did not correlate with the changes observed in previously studied corneal diseases nor did they correlate with genes encoding major structural proteins of the cornea.


CONCLUSIONS
Murine CCT has been measured with a variety of different techniques, but only among a limited number of different strains. Here, pachymetry was established as an additional tool and used to conduct a broad survey of different strains of inbred mice. These results demonstrated that murine CCT was highly influenced by genetic background and established a baseline for future genetic approaches to further elucidate mechanisms regulating CCT and its disease associations.
Lively
Geoffrey D
GD
Department of Molecular Physiology and Biophysics, The University of Iowa, Iowa City, Iowa, USA.
Jiang
Bing
B
Hedberg-Buenz
Adam
A
Chang
Bo
B
Petersen
Greg E
GE
Wang
Kai
K
Kuehn
Markus H
MH
Anderson
Michael G
MG
D000818:Animals; D002452:Cell Count; D003315:Cornea / Q000033:anatomy & histology* / Q000000981:diagnostic imaging / Q000502:physiology; D003319:Corneal Stroma / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D019573:Epithelium, Corneal / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000502:physiology; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains / Q000235:genetics*; D046529:Microscopy, Electron, Transmission; D020411:Oligonucleotide Array Sequence Analysis; D019655:Quantitative Trait, Heritable; D014463:Ultrasonography
D005136:Eye Proteins