Neurobiology and the function ofIntracellular FGFs(iFGFs):Intracellular Fibroblast Growth Factors (iFGFs) are important regulators of the activity of many different neurons in the brain and throughout the body. FGF14 is one of four iFGF genes. When the Ornitz laboratory completely inactivated the FGF14 gene in mice (FGF14 knockout mouse), the mice developed an ataxia syndrome in which they were uncoordinated, showed spontaneous abnormal movements (called paroxysmal dystonia) and occasionally had a tremor. The published phenotype of the FGF14 knockout mouse directly led to the discovery of a mutation in the FGF14 gene in a large human family in which affected individuals have a progressive spinocerebellar ataxia, which is now classified as SCA27. One major difference between the existing mouse model and the human disease is that the knockout mice completely lack a functional FGF14 gene whereas affected humans have one normal copy of the FGF14 gene and one mutant copy. Thus, although the existing mouse model and human disease phenotypes resemble each other, the underlying molecular mechanism that causes the disease in knockout mice and humans must be different. The Ornitz laboratory, with expertise in making and studying mouse models, is collaborating with the Nerbonne laboratory, with expertise in neurophysiology, to understand the mechanism of how FGF14 regulates the activity (excitability) of neurons and why when FGF14 is completely missing, mice develop an ataxia syndrome. A key question that we will answer is how a single mutation in one copy of human FGF14 results in a very similar disease to mice that are missing both copies of their FGF14 genes. Click on photo to right for Related publications:
Fgf14
expression during cerebellar development: "We demonstrate
that these isoforms have differential subcellular localization and
that they are differentially expressed in various adult tissues.
Using in situ hybridization we show that Fgf14 is widely
expressed in brain, spinal cord, major arteries and thymus between
12.5 and 14.5 days of mouse embryonic development...".
Please click the image at right for illustration.
This website is
maintained by Sharon Thomas: sthomas24@wustl.edu. Latest
update to this page: April 2008.
(iFGFs):Intracellular Fibroblast Growth Factors (iFGFs) are important regulators of the activity of many different neurons in the brain and throughout the body. FGF14 is one of four iFGF genes. When the Ornitz laboratory completely inactivated the FGF14 gene in mice (FGF14 knockout mouse), the mice developed an ataxia syndrome in which they were uncoordinated, showed spontaneous abnormal movements (called paroxysmal dystonia) and occasionally had a tremor. The published phenotype of the FGF14 knockout mouse directly led to the discovery of a mutation in the FGF14 gene in a large human family in which affected indiv
iduals have a progressive spinocerebellar ataxia, which is now classified as SCA27. One major difference between the existing mouse model and the human disease is that the knockout mice completely lack a functional FGF14 gene whereas affected humans have one normal copy of the FGF14 gene and one mutant copy. Thus, although the existing mouse model and human disease phenotypes resemble each other, the underlying molecular mechanism that causes the disease in knockout mice and humans must be different. The Ornitz laboratory, with expertise in making and studying mouse models, is collaborating with the Nerbonne laboratory, with expertise in 
