title: A mutation in the canine gene encoding folliculin-interacting protein 2 (FNIP2) associated with a unique disruption in spinal cord myelination.
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.
authors.affiliation: Institute for Genetic Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, California.|Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Pemberton
authors.affiliation: Institute for Genetic Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, California.
authors.forename: Sunju
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Mayer
authors.affiliation: Institute for Genetic Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, California.|Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Fang-Yuan
authors.initials: FY
authors.lastname: Li
authors.affiliation: Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Nolan
authors.initials: N
authors.lastname: Gokey
authors.affiliation: Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: John
authors.initials: J
authors.lastname: Svaren
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California Davis, Davis, California.
authors.forename: Noa
authors.initials: N
authors.lastname: Safra
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California Davis, Davis, California.
authors.forename: Danika L
authors.initials: DL
authors.lastname: Bannasch
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Katrina
authors.initials: K
authors.lastname: Sullivan
authors.affiliation: College of Veterinary Science, North Carolina State University, Raleigh, North Carolina.
authors.forename: Babetta
authors.initials: B
authors.lastname: Breuhaus
authors.affiliation: Institute for Genetic Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, California.|Division of Biomedical Sciences, Herman Ostrow School of Dentistry of USC, University of Southern California, Los Angeles, California.
authors.forename: Pragna I
authors.initials: PI
authors.lastname: Patel
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Duncan
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D003711:Demyelinating Diseases / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D004285:Dogs; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D066298:In Vitro Techniques; D008137:Longitudinal Studies; D008297:Male; D009154:Mutation / Q000235:genetics*; D009186:Myelin Sheath / Q000473:pathology*; D009836:Oligodendroglia / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000254:growth & development / Q000473:pathology*; D014202:Tremor / Q000209:etiology / Q000235:genetics / Q000662:veterinary; D014617:Vacuoles / Q000473:pathology
chemical_list: D002352:Carrier Proteins
keywords: FNIP2; Weimaraner; autosomal recessive; hypomyelination