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Changes in size of motor axons in hereditary canine spinal muscular atrophy.

Hereditary canine spinal muscular atrophy (HCSMA), a dominantly inherited disorder of motor neurons, has three phenotypes: accelerated, intermediate, and chronic. In the accelerated and intermediate phenotypes, axonal sizes in ventral roots were smaller than in controls. Reductions in axonal size occurred primarily in large axons, and the frequency of small-caliber axons was increased. In HCSMA, nerve fiber shape, i.e., circularity, was reduced, and the relative thickness of the myelin sheath as a function of axonal caliber was decreased. The density of fibers in motor nerves was increased, making it unlikely that a selective loss of large-caliber axons explained the increased frequency of small-caliber axons. These observations suggest that, in HCSMA, changes in axonal size in motor nerves are associated with both growth arrest and axonal atrophy.