The goal of this research project is to test the hypothesis that voltage gated sodium channel beta subunits are cell adhesion molecules in vivo, and are involved in the formation of nodes of Ranvier as well as the recruitment of other molecules involved in the nodal signaling complex. An alternative model system using Zebrafish is being generated in our laboratory. First, the sodium channel beta subunits in Zebrafish will be cloned and characterized using an in vitro system and electrophysiological techniques. Preliminary data show that Zebrafish have beta subunits orthologous to higher vertebrates as well as novel subunits not previously characterized. Next, """"""""knock down"""""""" fish will be generated which will allow us to examine the role of beta subunits in vivo using antisense RNA techniques. Finally, a dominant negative beta1subunit will be used to test the ability of the beta1subunit to recruit ankyrin to the plasma membrane. Understanding the mechanism of node of Ranvier formation is important to elucidating the mechanisms of demyelinating disease. Demyelinating diseases are characterized by a loss of myelin and an impairment of action potential conduction as nodes of Ranvier are lost. Understanding nodal formation can contribute to clarifying the triggers for demyelinating disease as well as potential therapies. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31NS047901-01A1
Application #
6836112
Study Section
Special Emphasis Panel (ZRG1-F03B (20))
Program Officer
Stewart, Randall R
Project Start
2004-09-01
Project End
2007-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$33,382
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pharmacology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Fein, Amanda J; Wright, Melissa A; Slat, Emily A et al. (2008) scn1bb, a zebrafish ortholog of SCN1B expressed in excitable and nonexcitable cells, affects motor neuron axon morphology and touch sensitivity. J Neurosci 28:12510-22
Fein, Amanda J; Meadows, Laurence S; Chen, Chunling et al. (2007) Cloning and expression of a zebrafish SCN1B ortholog and identification of a species-specific splice variant. BMC Genomics 8:226