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Cloning of M-calpain 80 kD subunit from the axonal degeneration-resistant WLDs mouse mutant

✍ Scribed by Jonathan D. Glass; Norman Nash; Ian Dry; Deborah Culver; Allan I. Levey; Steven Wesselingh


Book ID
101245597
Publisher
John Wiley and Sons
Year
1998
Tongue
English
Weight
204 KB
Volume
52
Category
Article
ISSN
0360-4012

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✦ Synopsis


Calpains are calcium-activated cysteine proteases that are involved in cellular degradation in models of neurodegeneration. Calpains are the effectors of cytoskeletal disruption during axonal degeneration, a pathological feature of many neurological disorders. The WLD S mouse mutant is resistant to axonal degeneration and demonstrates prolonged survival of the cytoskeleton after nerve injury. To investigate the possibility that a mutation in calpain or abnormalities in calpain protein expression is responsible for the resistance to axonal degeneration seen in the WLD S mouse mutant, we 1) cloned and sequenced the large subunit of the high calcium-requiring form of calpain (m-calpain) from nervous system tissues of WLD S and from wild-type C57BL/6 mice, and 2) generated polyclonal m-calpain antibodies for comparison of relative protein levels by Western blot. We found our sequence for mouse m-calpain to be almost identical to another recently published mouse sequence, and the wild-type and WLD S sequences to be identical. Our fusion protein and peptide polyclonal antibodies were specific for the 80 kD subunit and recognized appropriate protein bands from pure m-calpain, fusion protein, and in tissue. There was no apparent difference in m-calpain expression in nerve or spinal cord in noninjured adult animals. These data suggest that a defect in m-calpain 80 kD subunit does not likely underlie the WLD S phenotype, but raise questions about other subunits of calpain and possibly other proteases.