Recently many neuropathological mutant mice have been reported. By comparing the results of analysis of mutant mice with control animals, we can obtain an enormous amount of knowledge. I have focused mainly on the mutants which have abnormality in the myelin formation which is a typical example of neuron-glia interrelationship, and then focused on the cerebella mutant. Both shiverer and myelin deficient (mid) are allelic mutant and are characterized by poor myelin formation accompanying intentional tremor and ataxic movement. Shiverer is known to be a deletion mutant of myelin basic protein (MBP) gene. We found that in mid MBP gene is duplicated and the reduced expression is mainly determined by the level of mRNA. The promoter activity of the two MBP genes in mid is similar. Two genes are tandemly arranged in chromosome 18, and in the gene located at the 5' region shows inversion within the gene. The abnormal rearrangement of the MBP gene is the cause of the reduced expression of MBP. The jimpy mutant, an X-linked recessive dysand de-myelinating mutant, has been shown to contain abnormal myelin proteolipid protein mRNA. To understand the molecular basis of the mutation, we analyzed the structure of proteolipid protein (PLP) mRNA by an RNase-mapping procedure, using the probes specific to each exon of the mouse PLP gene. We found that the fifth exon of the PLP gene is not unilized in the jimpy. In the cerebellar mutant, staggerer, P₄₀₀ protein, a cerebellum-characteristic protein, was found to be markedly reduced. In the staggerer mutant, the synapses between parallel fibers and dendritic spines on the Purkinje cells are missing, spiny branchlets are absent and the arborization of the Purkinje cell becomes abnormally simplified. P₄₀₀ protein was a convanavalin A-binding, 250-kDa glycoprotein, which was shown to be enriched in Purkinje cells. These results made P₄₀₀ protein a candidate for a cell surface recognition molecule which account for the early specification of the parallel fiber-Purkinje cell synapses.

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