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Glia. 2014 Jan;62(1):39-51. doi: 10.1002/glia.22582.

A mutation in the canine gene encoding folliculin-interacting protein 2 (FNIP2) associated with a unique disruption in spinal cord myelination.

Author information

1
Institute for Genetic Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, California.
2
Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada.
3
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin.
4
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin.
5
Department of Population Health and Reproduction, School of Veterinary Medicine, University of California Davis, Davis, California.
6
Department of Medicine, University of Washington, Seattle, Washington.
7
College of Veterinary Science, North Carolina State University, Raleigh, North Carolina.
8
Division of Biomedical Sciences, Herman Ostrow School of Dentistry of USC, University of Southern California, Los Angeles, California.
#
Contributed equally

Abstract

Novel mutations in myelin and myelin-associated genes have provided important information on oligodendrocytes and myelin and the effects of their disruption on the normal developmental process of myelination of the central nervous system (CNS). We report here a mutation in the folliculin-interacting protein 2 (FNIP2) gene in the Weimaraner dog that results in hypomyelination of the brain and a tract-specific myelin defect in the spinal cord. This myelination disruption results in a notable tremor syndrome from which affected dogs recover with time. In the peripheral tracts of the lateral and ventral columns of the spinal cord, there is a lack of mature oligodendrocytes. A genome-wide association study of DNA from three groups of dogs mapped the gene to canine chromosome 15. Sequencing of all the genes in the candidate region identified a frameshift mutation in the FNIP2 gene that segregated with the phenotype. While the functional role of FNIP2 is not known, our data would suggest that production of truncated protein results in a delay or failure of maturation of a subpopulation of oligodendrocytes.

KEYWORDS:

FNIP2; Weimaraner; autosomal recessive; hypomyelination

PMID:
24272703
PMCID:
PMC4026025
DOI:
10.1002/glia.22582
[Indexed for MEDLINE]
Free PMC Article

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