Ataxia and paroxysmal dyskinesia in mice lacking axonally transported FGF14

Qing Wang, Mark E. Bardgett, Michael Wong, David F. Wozniak, Junyang Lou, Benjamin D. McNeil, Chen Chen, Anthony Nardi, David C. Reid, Kelvin Yamada, David M. Ornitz

Research output: Contribution to journalArticlepeer-review

148 Scopus citations

Abstract

Fibroblast growth factor 14 (FGF14) belongs to a distinct subclass of FGFs that is expressed in the developing and adult CNS. We disrupted the Fgf14 gene and introduced an Fgf14N-β-Gal allele that abolished Fgf14 expression and generated a fusion protein (FGF14N-β-gal) containing the first exon of FGF14 and β-galactosidase. Fgf14-deficient mice were viable, fertile, and anatomically normal, but developed ataxia and a paroxysmal hyperkinetic movement disorder. Neuropharmacological studies showed that Fgf14-deficient mice have reduced responses to dopamine agonists. The paroxysmal hyperkinetic movement disorder phenocopies a form of dystonia, a disease often associated with dysfunction of the putamen. Strikingly, the FGF14N-β-gal chimeric protein was efficiently transported into neuronal processes in the basal ganglia and cerebellum. Together, these studies identify a novel function for FGF14 in neuronal signaling and implicate FGF14 in axonal trafficking and synaptosomal function.

Original languageEnglish
Pages (from-to)25-38
Number of pages14
JournalNeuron
Volume35
Issue number1
DOIs
StatePublished - Jul 3 2002

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