Developmental Changes in Gene Expression in the Visual Cortex of Mice with Retinal Degeneration

Retinal degeneration can be caused by many genetic mutations. The Pde6b-mutation affects rod photoreceptors, which are list in mice by post-natal day (PND) 21 (Marc et al., 2003: Chang et al., 2002). Mice that are homozygous for the Pde6b-mutation are born with vision and go blind over time. Behavioural studies suggest that Pde6b- mice lose their visual activity by age PND 42 and subsequently lose their ability to detect differences in light illumination by PND 100. Behavioral changes have been correlated with changes in gene expression in specific cells in earlier studies. In this study, gene expression changes were examined for astrocytes in the visual cortex using real-time PCR for astrocyte-specific genes GFAP, Vimentin adn S100. GFAP and vimentin have been found to be useful for identifying the link between behavioral changes and their corresponding gene expression pattern changes (Kafitz et al., 1999). S100 MRNA expression is also useful because it can influence GFAP and Vimentin at teh protein level (Muller Et al., 1993). It was hypothesized that astrocyte-specific gene expression changes will be found at relevant ages (PND 21, 42, and 100) in astrocytes of the visual cortex in our Pde6b- mice compared to Pde6b+ mice, due to remodeling after a loss of visual function idicated by behavioral changes at these ages. We hypothesize that GFAP expression will decrease, vimentin expression will icrease and we are not sure what will happen to the expression of S100 at these relevant ages. Results suggest that changes in gene expression are takingplace at PND 7, 21, and 49. Our hypothesis may not be fully supported at the ages where behaviors were changing, but our data do suggest changes in gene expression at other possibly relevant ages. PND 21 was the age that showed a change in gene expression for vimentin coinciding with the age that rod photoreceptors are lost. This age could be examined further at the protein level for the glial genes.Master'sCollege of Arts and Sciences: BiologyUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/117690/1/Cornett.pd