Hypomyelinated mutant mice. II. Myelination in vitro

Abstract

Organotypic cultures of cerebellum from hypomyelinated mutant mice provide a powerful experimental system for studying the cell biology of the mutant diseases. We have examined the extent to which the culture system reproduces the diseases of three well-known mutants, qk, jpmsd, and jp. Quantitation of myelin profiles per sq. mm of section demonstrates that in vitro, as in situ, qk produces the most myelin jpmsd an intermediate amount, and jp the least. Myelin in qk cultures is unique in being invisible by light microscopy of the living culture. Hypomyelination of jp may be more severe in vitro than in situ. Cultures of jpmsd exhibit many of the ultrastructural features of cerebellar abnormalities that occur in situ: degree of hypomyelination, clustering of myelin segments, scarcity of oligodendrocytes, absence of nodes of Ranvier but presence of heminodes, and apparent structural integrity of the myelin sheaths. Correspondence between in vitro and in situ ultrastructure is more difficult to assess for jp, because the available sample of jp myelin in vitro is too small, and for qk, because the abnormalities observed in situ resemble nonspecific abnormalities of normal myelin in vitro.