Canine degenerative myelopathy (DM) is a neurodegenerative disease in dogs with similarities in genetics and phenotype to some forms of ALS in humans. In 2008, a team of researchers at University of Missouri in Columbia with collaborators at The Broad Institute of MIT/Harvard in Cambridge, MA, found a link between DM and mutations in SOD1(see Nov 2008 news), which also causes approximately 20% of familial ALS cases. Strikingly, not all dogs homozygous for the SOD1 mutation developed disease.
In the May 16 PNAS, a team of researchers led by Kerstin Lindblad-Toh of Uppsala University in Sweden report that SP110 variants affect both age of onset and penetrance of DM, based on a results of a genome-wide association study in SOD1-homozygous dogs that either exhibited the disease phenotype or were non symptomatic. SP110 is a multi-protein complex that regulates gene transcription in leukocytes, and the identified variants modify expression of its various isoforms in blood cells. These findings providing a genetic link between immune system dysfunction and the pathogenesis of ALS, and raise further questions about how SP110 modifies the course of disease in dogs, and potentially in humans.
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Ivansson EL, Megquier K9, Kozyrev SV, Murén E, Körberg IB, Swofford R, Koltookian M, Tonomura N, Zeng R, Kolicheski AL, Hansen L, Katz ML, Johnson GC, Johnson GS, Coates JR, Lindblad-Toh K. Variants within the SP110 nuclear body protein modify risk of canine degenerative myelopathy. Proc Natl Acad Sci U S A. 2016 May 16. [Pubmed].