Neurofilaments of Klotho, the mutant mouse prematurely displaying symptomsresembling human aging

We reported previously that neurofilaments (NFs) of aged rats were highly p acked in the axon and contained a smaller amount of NF-M as compared with t hose of young rats (Uchida et al. [1999] J. Neurosci. Res. 58,337-348), We studied NFs of the mutant mouse, named Klotho, which displays prematurely s ymptoms resembling human aging. The transport of axonal cytoskeletal protei ns, including NFs, tubulin and actin, was decreased at the leading portion of the peak of transported proteins in Klotho during the process of prematu re aging. The nearest neighbor inter-NF distance in Klotho axone (35-39 nm) was shorter than that of the wild-type mouse (48-49 nm), indicating the pa cking of NFs in Klotho. The ratio of NF-M to NF-L was slightly decreased in cytoskeletons from the spinal cords of Klotho. These changes ave similar, though not identical, to those observed in aged rats, and are the first evi dence of age-related changes in the neurons of Klotho. (C) 2001 Wiley-Liss, Inc.