The cellular distribution of the Wlds chimeric protein and its constituent proteins in the CNS

The C57BL/Wlds mouse is a mutant strain of mouse that shows greatly slowed Wallerian degeneration both in the central and peripheral nervous system. Using immunohistochemistry, immunofluorescence and Western blotting, we have investigated the distribution of the chimeric Wlds protein and its different components in neurons of the CNS of Wlds mice and wild-type C57BL/6J mice. The expression of the Wlds protein is restricted to the nucleus in Wlds mice. Wlds was not detected in axons. The Wlds mice express both the normal and chimeric forms of ubiquitination factor E4 (Ube 4b) and nicotinamide mononucleotide adenylyltransferase-1 (Nmnat-1). The normal forms were expressed both in the cytoplasm and the nuclei of neurons in Wlds mice and wild-type mice, and were also present in the axon. The normal form of Ube4b, mono- and poly-ubiquitin and IκBα, a substrate of Ube4b, were not differentially expressed in Wlds mice compared with wild-type mice. However, the expression of both the normal and mutant forms of Nmnat-1 was higher in the nuclei of Wlds mice compared with wild-type mice. Therefore, axon protection in Wlds mice does not appear to be controlled by expression of Wlds protein in the axons per se and also is unlikely to be related to the different activity of Ube4b either in general ubiquitination or toward this particular substrate. The increased Nmnat-1 activity in the nucleus of Wlds mice compared with wild-type mice seems to be a significant factor in the axon protection. It is not known whether the expression of the Nmnat-1 in the axon is significant.