PMC:1142324 / 5995-8838 JSONTXT

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These results suggest that the ADAM22 mRNA expression is neuronal in the mouse CNS.\nBased on the mRNA distribution pattern, we performed immunohistopathological analysis of the cerebellum and hippocampus extensively. Despite the high level of expression of ADAM22 mRNAs in the cerebellar granule cells, granule cell layer was normally formed and Purkinje cell morphology (calbindin-staining) of the mutant mouse looked intact (Figs. 4A–D). Hippocampal formation was also normally formed (Figs. 4I–J). These results suggest that neuronal cell migration was not impaired in the mutant mouse. Myelin-formation detected by MBP (myelin basic protein) staining of the mutant in the cerebellum (Fig. 4H) and spinal cord (Fig. 4L) was also indistinguishable with the wild-type littermate (Figs. 4G,K). In summary, we could not find any signs of abnormalities in the mutant mouse brain by the light microscopic examination.\nNext, the spinal cord and peripheral nerves of each genotype were analysed by toluidine blue stain, which reveals myelin formation. Surprisingly, lack of myelin or thin myelin was observed in the sciatic nerves (Fig. 5B) and trigeminal nerves (Fig. 5D) in homozygous mutants. Because no lesions were observed in the spinal cord (Fig. 5F), it was suggested that Schwann cell specific myelination defect occurred in the homozygous mice. To analyse the state of myelinating Schwann cells and axons, electron microscopic (EM) analysis of the sciatic nerve was performed (Fig. 6). Schwann cells formed thin or no myelin in the homozygous mutant (Fig. 6B). In contrast, heterozygous mice showed complete myelination (Fig. 6A). Morphology of the axons looked normal in each genotype. Immunohistochemical analysis of the sciatic nerve showed that increased number of nuclei (Fig. 7B) and reduced staining of MBP (Fig. 7D) were remarkable in the homozygous mutant. The Schwann cell marker, S100 staining signal was intensely observed in the homozygote as well as wild-type (Figs. 7E, F). These results suggest that proliferation of the Schwann cells was not impaired but differentiation is severely delayed in the ADAM22-deficient 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