Interrupted nerve fibres from the C57BL/Ola strain of mouse degenerate after an extraordinary delay compared to nerves of standard laboratory mice. Other investigators, using electrophysiologic methods, concluded that the mutant phenotype diminishes with age, implying that the mutation in C57BL/Ola mice affects a developmentally regulated gene. In an effort to confirm this observation, we studied the course of Wallerian degeneration in C57BL/Ola mice aged 1 through 16 months by using quantitative morphometry, immunohistochemistry, and immunoblotting, but found the period of axonal survival after nerve transection to be no different in old versus young C57BL/Ola mice. We conclude that the C57BL/Ola phenotype of prolonged survival of transected nerves is not affected by age, although certain physiologic measures may degrade in older animals. The persistence of axoplasm after nerve injury in C57BL/Ola mice may be the feature most closely related to the function of the mutant gene.

The C57BL/Ola (Ola) mouse is a mutant substrain in which transected axons undergo very slow Wallerian degeneration. Because axonal degradation during Wallerian degeneration is calcium dependent, we tested whether Ola axons are susceptible to calcium-mediated axonal degeneration by comparing neurofilament degradation between Ola and C57BL/6 mice in sciatic nerve explants. Using immunoblot analysis of neurofilament degradation and electron microscopy we found that as in normal axons, axonal degeneration in the Ola is calcium dependent. However, when compared with normal animals, higher levels of calcium were required for complete degradation of neurofilaments in Ola nerve, suggesting a relative insensitivity to calcium-mediated degeneration in the Ola. We conclude that calcium-activated proteases are present and active in Ola axons but that higher levels of calcium are required to accomplish complete axonal degradation. These results suggest a possible mechanism for prolonged survival of transected Ola axons and provide potential insight into the pathophysiology of axonal degeneration in injury and disease.

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