We are studying CNS myelin development, using the single gene mutations (jp, jp(msd), qk, shi, shi(mld) which impair CNS myelination in the mouse. The myelin defects are reproduced in organotypic of cerebellum, but can be """"""""cured"""""""" by introducing normal optic nerve into the cultures as a source of normal oligodendroglia. Cultures of normal cerebellum, stripped of resident oligodendroglia by mitonic inhibitors, will also accept myelination by introduced normal optic nerve glia. We plan to define the details of mitosis, migration, maturation, and myelination of normal oligodendroglia in this culture system: to study the corresponding in vitro properties of mutant optic nerve glia; to study the abnormal shapes of mutant oligodendroglia in Golgi impregnations and serial section reconstructions; to study the morphology of double mutant mice (shi + jp) which have been discovered to have unexpected biochemical properties; and to inaugurate culture studies of a newly discovered mutation. Methods employed will be tissue culture, light and electron microscopy, immunohistochemistry, 3H-thymidine autoradiography, computer-aided 3-dimensional reconstruction, and practical genetics. The goal is to define the role of the wild-type DNA normally present at the mutant loci, which is part of the genetic program for CNS myelin formation and maintenance.
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