Research article - Peer-reviewed, 2009
Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis
Awano, Tomoyuki; Johnson, Gary S.; Wade, Claire M.; Katz, Martin L.; Johnson, Gayle C.; Taylor, Jeremy F.; Perloski, Michele; Biagi, Tara; Baranowska, Izabella; Long, Sam; March, Philip A.; Olby, Natasha J.; Shelton, G. Diane; Khan, Shahnawaz; O'Brien, Dennis P.; Lindblad-Toh, Kerstin; Coates, Joan R.Abstract
Canine degenerative myelopathy (DM) is a fatal neurodegenerative disease prevalent in several dog breeds. Typically, the initial progressive upper motor neuron spastic and general proprioceptive ataxia in the pelvic limbs occurs at 8 years of age or older. If euthanasia is delayed, the clinical signs will ascend, causing flaccid tetraparesis and other lower motor neuron signs. DNA samples from 38 DM-affected Pembroke Welsh corgi cases and 17 related clinically normal controls were used for genome-wide association mapping, which produced the strongest associations with markers on CFA31 in a region containing the canine SOD1 gene. SOD1 was considered a regional candidate gene because mutations in human SOD1 can cause amyotrophic lateral sclerosis (ALS), an adult-onset fatal paralytic neurodegenerative disease with both upper and lower motor neuron involvement. The resequencing of SOD1 in normal and affected dogs revealed a G to A transition, resulting in an E40K missense mutation. Homozygosity for the A allele was associated with DM in 5 dog breeds: Pembroke Welsh corgi, Boxer, Rhodesian ridgeback, German Shepherd dog, and Chesapeake Bay retriever. Microscopic examination of spinal cords from affected dogs revealed myelin and axon loss affecting the lateral white matter and neuronal cytoplasmic inclusions that bind anti-superoxide dismutase 1 antibodies. These inclusions are similar to those seen in spinal cord sections from ALS patients with SOD1 mutations. Our findings identify canine DM to be the first recognized spontaneously occurring animal model for ALS.Published in
Proceedings of the National Academy of Sciences2009, volume: 106, number: 8, pages: 2794-2799
Authors' information
Awano, Tomoyuki
University of Missouri
Johnson, Gary S.
University of Missouri
Wade, Claire M.
Massachusetts Institute of Technology (MIT)
Katz, Martin L.
University of Missouri
Johnson, Gayle C.
University of Missouri
Taylor, Jeremy F.
University of Missouri
Perloski, Michele
Massachusetts Institute of Technology (MIT)
Biagi, Tara
Baranowska, Izabella (Baranowska, Izabella)
Swedish University of Agricultural Sciences, Department of Animal Breeding and Genetics
Long, Sam
University of Pennsylvania
March, Philip A.
Tufts University
Olby, Natasha J.
North Carolina State University (NC State)
Shelton, G. Diane
University of California San Diego
Khan, Shahnawaz
University of Missouri
O'Brien, Dennis P.
University of Missouri
Lindblad-Toh, Kerstin
Coates, Joan R.
University of Missouri
UKÄ Subject classification
Genetics
Publication Identifiers
DOI: https://doi.org/10.1073/pnas.0812297106
URI (permanent link to this page)
https://res.slu.se/id/publ/28386