Hereditary canine spinal muscular atrophy is phenotypically similar but molecularly distinct from human spinal muscular atrophy

Hereditary canine spinal muscular atrophy (HCSMA) is an autosomal dominant motor neuron disease that is similar in pathology and clinical presentation to various forms of human motor neuron disease. We have tested the hypothe sis that the canine survival motor neuron (SMN) gene is responsible for HCS MA by genetic and molecular analysis of a colony of mixed breed dogs, all d escended from a single affected individual. We cloned the canine SMN gene a nd determined the DNA sequence in an affected and an unaffected dog. We fou nd no germline mutations in the SMN gene of the affected individual. Using conventional linkage analysis with canine-specific microsatellite repeat ma rkers we screened the canine genome and identified a single linkage group l ikely to contain the HCSMA gene. Analysis with a panel of canine/rodent hyb rid cell lines revealed that the SMN gene did not map to the same chromosom e as the HCSMA linkage group. Collectively these results suggest that the m olecular basis for HCSMA is distinct from that of phenotypically similar hu man disorders caused by inherited mutations in the SMN gene. This further s uggests that additional studies on the molecular nature of HCSMA may reveal an unknown element of the molecular pathway leading to motor neuron diseas e.