Studies of Kinesins and Axonal Transport in a Mouse Model of NF1
Final rept. 15 Feb 2007-14 Feb 2008
CATHOLIC HEALTHCARE WEST PHOENIX AZ
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In this research project, we investigated the hypothesis that mutation of the NF1 gene might alter axonal and dendritic transport in neurons. This might provide new insights into the development of cognitive defects in patients with neurofibromatosis 1. The significant results of this pilot research project are all derived from functional studies done by sciatic nerve ligation in wild-type and Nf1- mice. After nerve ligation, proximal and distal segments of the sciatic nerve were homogenized, and analyzed for content of tubulin and synaptic proteins by Western blot and immunohistochemistry. Out results support the idea that there is a quantitative decrease in the accumulation of synaptic proteins immediately proximal to the site of nerve ligature in the Nf- nerve, as compared to wild-type nerves. This supports the idea that Nf1 gene mutation does indeed result in a quantitative defect in axonal transport in the peripheral nervous system. We are preparing to see if there is a similar deficiency in the rate of axonal transport in the central nervous system CNS as well. Once we can confirm these findings in the CNS, then we shall embark on a series of experiments that address the molecular mechanisms by which axonal transport is affected in the Nf1- mice.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research