Abstract:
The pathogenesis underlying peripheral nerve damage remains unclear. Recent microarray studies in our lab investigating
dorsal root ganglia (DRG) gene alterations in diabetic neuropathy (DN) reveal that a novel gene, crystallin gamma-s (crygs), has the largest-fold reduction in expression (-7.38-fold, p<0.001). These results have led to the hypothesis that crygs may play a role in the pathogenesis of nerve damage. Crygs is a member of the crystallin family which consists of lens structural proteins. Recently, crygs has been discovered outside the lens, including retinal ganglion cells and the PIN2 prostate cancer cell line. Immunocytochemistry was performed to localize crygs protein in the DRG. Antibodies to crygs stained a subset of DRG neurons, with primarily nuclear localization. To assess the role of crygs in somatosensory function, we have investigated mice with a null mutation in the crygs locus (crygs -/-) as well as mice with a functionally mutated crygs protein (opj -/-). Analysis of a battery of sensory functions in both lines of mice reveals altered sensory function. Specifically, crygs -/- display abnormalities in mechanical responsiveness to von Frey monofilament stimulation, whereas opj -/- display deficits in mechanical and thermal thresholds, as well as overall locomotor activity. Sensitivity to cold stimuli was normal in both lines. These results reveal that normal crygs expression and function is required for appropriate somatosensation. Additionally, alterations in crygs expression in DN strengthens the idea that crygs may play an important role in the pathogenesis of abnormal sensation in various disease settings.
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