Genetic analysis of a spontaneous canine model of primary progressive multiple sclerosis

DNA analysis of the Dog Leukocyte Antigen (DLA) MHC II region, specifically, DRB1, DQB, DQA and Myelin Basic Protein (MBP) gene was performed on both healthy German Shepherd dogs (GSD) and GSD presenting with clinically diagnosed Degenerative Myelopathy (DM), a chronic progressive neurological disease that appears to be autoimmune related. Analysis was performed to demonstrate DM as genetically linked and analogous to primary progressive Multiple Sclerosis (PPMS) in human beings. PPMS has been found to be genetic in nature and linked to the Human Leukocyte Antigen (HLA) at the DRB1 region. Analysis of the DLA‐DRB1 was performed using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and direct sequencing. RFLP analysis of the 285bp PCR product produced identical results in all dogs tested suggesting them to be homozygous for DLA‐DRB1 allele*1101. Further analysis of the PCR product by sequencing confirmed the presence of DLA‐DRB1 *1101, and revealed a homozygous point located at hypervariable region 2 (HVR2) of the DLA‐DRB1 allele*1101 of GSD with DM. Healthy GSD were found to be heterozygous at this point suggesting the homozygous point to be unique in DM. PCR was also performed on the MBP gene and product size was analyzed to determine alleles present. The MBP allele consisting of a 70 bp tandem repeat (TGGA) deletion was found in 88% of DM dogs tested and only in 57% of healthy GSD. This deletion correlates to the same deletion found in a population of multiple sclerosis (MS) patients in Finland. DNA evidence found suggests DM has a genetic basis similar to PPMS in human beings.