Global gene expression analysis of lenses from different mouse strains and in the alpha3Cx46 knockout mouse.

PURPOSE

Disruption of the mouse gene encoding the gap junction subunit alpha3 connexin 46 (alpha3Cx46) results in the formation of lens cataracts that have a severity affected by the genetic background of the mouse strain. To identify the genes that influence the severity of the nuclear opacity, global gene expression was analyzed in lenses from the 129SvJae strain and compared to the C57BL/6J strain.

METHODS

Lens transcripts were subjected to cDNA microarray analysis. Results on selected genes were confirmed by real-time PCR.

RESULTS

GENES THAT WERE DETERMINED TO BE ALTERED IN EXPRESSION LEVELS AS A RESULT OF STRAIN DIFFERENCES COULD BE CLUSTERED INTO THREE GROUPS: energy metabolism, stress response, and cell growth.

CONCLUSIONS

There were no observed changes in gene expression as a result of the lack of alpha3Cx46 in the different mouse strains, suggesting that the pathways mediated by this connexin do not influence gene transcription in the lens. Analysis of the transcript changes due to strain differences provides new insights into potential genetic modifiers of cataractogenesis. More detailed experimentation will be needed to determine if these observed changes do indeed affect cataractogenesis.