Function of FGF14 in progressive spinocerebellar ataxia

2007 Pilot Project Read More

Investigators

Principal Investigator: David Ornitz, MD, PhD (WUSTL Developmental Biology)
Co-investigators: Kel Yamada, MD (WUSTL Neurology), Jeanne Nerbonne, PhD (WUSTL Developmental Biology), David Wozniak, PhD (WUSTL Psychiatry)

Description

Patients with spinocerebellar ataxias (SCAs) experience a loss of muscle control in their arms and legs, with resulting loss of balance and coordination. Patients with SCA type 27, a dominantly-inherited condition, have progressive ataxia as well as mental retardation. SCA27 is caused by a single-gene mutation in the gene encoding fibroblast growth factor 14 (FGF14). An animal model lacking FGF14 function shows similar behavior. This project will fully characterize the degenerative phenotype in FGF14-deficient animals. Additionally, these investigators will generate an animal model which more closely resembles the genetics of the human disease, to reveal the molecular mechanisms which lead from FGF14 mutation to degeneration of cerebellar neurons.

Funded Grants

“FGF14 in the regulation of Purkinje neuron excitability and SCA27
NIH-NINDS, R01NS065761-01 (Ornitz, PI)
The molecular, cellular and physiological studies proposed will provide new and fundamentally important insights into the functional roles of FGF14 in regulating neuronal excitability and into the underlying molecular mechanisms by which mutations in FGF14 cause disease in humans.

Intellectual Property

FGF14 mutant mouse, SCA27

Publications

Laezza, F., Lampert, A., Kozel, M.A., Gerber, B.R., Rush, A.M., Nerbonne, J.M., Waxman, S.G., Dib-Hajj, S.D., and Ornitz, D.M. (2009). FGF14 N-Terminal Splice Variants Differentially Modulate Nav1.2 and Nav1.6-Encoded Sodium Channels. Mol Cell Neurosci 42, 90-101.

Shakkottai, V.G., Xiao, M., Xu, L., Wong, M., Nerbonne, J.M., Ornitz, D.M., and Yamada, K.A. (2009). FGF14 regulates the intrinsic excitability of cerebellar Purkinje neurons. Neurobiol Dis 33, 81-88.

Xiao, M., Bosch, M.K., Nerbonne, J.M., and Ornitz, D.M. (2013). FGF14 localization and organization of the axon initial segment. Mol Cell Neurosci 56, 393-403.


Updated February 2014

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