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Corticotrophin releasing factor expression in the tottering and leaner mouse cerebellum

Michelle Browning

Objective-To compare corticotrophin releasing factor (CRF) expression in mice that carry mutations in the gene coding for the pore-forming protein of neuronal P/Q-type calcium ion channels, which result in various neurological disorders including cerebellar ataxia.

Animals- Male mice exhibiting various levels of genetically-induced cerebellar ataxia, with the following genotypes, wild type +/+, tottering tg/tg, and leaner tgla, being used.

Procedure- Cerebella were taken from anesthetized mice for use in either Western blotting or immunohistochemistry.  Western Blotting protocols were used to attempt to measure the levels of CRF in the cerebella of each of the three genotypes relative to a standard protein that is thought to be equally expressed in all cerebella.  Standart immunohistochemistry was used to visualize the location of CRF in cerebella from mice of all three genotypes

Results- Western blotting for the standard protein, neuron specific enolase, was successful, but CRF was not visualized using western blotting.  Immunohistochemstry revealed significant differences in expression levels between the three genotypes examined.  CRF expression in the cerebellum was decreased in tottering mice relative to wild type mice while CRF expression was increased in the leaner mice compared to wild type mice.

Conclusions And Clinical Relevance- Changes in CRF expression in these mutant mice are most likely related to the altered calcium channel function that these mice also exhibit.  It is possible that defective synaptic transmission that is predicted to occur in the cerebella of these mutant mice is influencing CRF expression, although the exact relationships still need to be elucidated.