Abstract
Abstract: :
Purpose: The Emory mouse is a well-characterized rodent model for age-onset cataract; however, the mechanisms underlying cataract formation in the Emory mouse are not clear. To identify those pathways that underlie cataractogenesis in the Emory mouse, we examined the gene expression profiles of pre-cataract and post-cataract Emory mouse lenses and we determined the tissue-specificity and developmental expression profiles of the identified transcripts. Methods: Eyes were extracted from late strain Emory mice at 3 weeks (pre-cataract) and 7.5 months (post-cataract) and lenses were examined for opacity and removed. Gene expression differences were identified by RT-PCR differential display and transcripts exhibiting altered levels of gene expression were cloned and identified by sequencing. Gene expression differences were confirmed by semi-quantitative RT-PCR. Identified transcripts were examined in 4 week up to 11.5 month old lenses from three non-Emory mouse strains (FVB/N, 129Sv and CD1) and their spatial expression patterns determined between the lens and the rest of the eye. Results: Three transcripts exhibited altered levels of gene expression between 3 week and 7.5 month old Emory mouse lenses. These encoded aA-crystallin (decreased), bA3/A1-crystallin (decreased) and ARK membrane receptor tyrosine kinase (increased). These alterations in gene expression were specific for the Emory mouse and were confined to the lens. Conclusions: The present data confirm that aA-crystallin gene expression is decreased in the Emory mouse lens relative to age-matched control lenses and they provide evidence for cataract- and lens-specific up-regulation of the ARK membrane receptor tyrosine kinase in the Emory mouse. The results suggest that phosphorylation and growth control pathways activated by increased levels of ARK may be important for the development of Emory mouse cataract.
Keywords: 338 cataract • 417 gene/expression • 309 aging