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This study compares peripheral myelination in a specific subdivision of the sciatic nerve of jp msd and unaffected littermate mice. No significant differences are found in numbers of myelinated and unmyelinated axons, diameters of axons, thickness of myelin sheaths relative to axon diameter, extent of unmyelinated axons segregation by Schwann cell processes, or in the ultrastructure of myelin and Schwann cells. By contrast, jp msd mutant mice show severe CNS hypomyelination. This evidence, that the jp msd mutation affects only oligodendrocytes, distinguishes mutations at this locus from others producing CNS hypomyelination in which PNS myelin is also affected.

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.

Mice which carry both the shiverer (shi) and the jimpy (jp) mutations have a morphological phenotype with features of each single mutation by itself but in milder form: the number of myelin sheaths is increased relative to jp, the thickness of sheaths and amount of major dense line is increased relative to shi, and the abnormal, lipid-filled cells characteristic of jp are not seen. However, the abnormal bundles of oligodendrocyte microprocesses and errors in the targeting of myelination which characterize shi are not altered by the presence of the jp mutation. This morphological evidence suggests partial reciprocal intergenic suppression in shiverer jimpy double mutant mice and therefore agrees with conclusions based on biochemical data presented by Kerner and Carson (Brain Research, 374 (1986) 45-53).

Indirect immunofluorescence was used to stain DR antigen and interleukin-2 receptor (Tac) of T-lymphocytes (Leu 4+). Tissue samples of synovial membrane were cut from arthroscopic biopsies of inflamed knees in four patients with active rheumatoid arthritis (RA). Consecutive cryostatic sections of rheumatoid sinovium were analysed using monoclonal antibodies. It was found that a high percentage of T-lymphocytes express DR antigen. In contrast the proportion of T cells expressing Tac was small. We conclude that T cell activation in synovial membrane is incomplete, and this disfunction may contribute to the chronic inflammation of RA.

Hypomyelinated mutant mice are valuable natural animal systems for analysis of CNS myelin development, chemistry and diseases. One mutant, jpmsd, has never received thorough morphological description. We here describe the detailed morphology of jpmsd, compare it with well-studied jp and qk on their present genetic backgrounds, and discuss the genetic histories of all 3 mutants. Region for region, jpmsd has twice as much myelin as jp, but 1/2--1/5 as much as qk. Both jp and jpmsd have scarce oligodendrocytes, rare nodes of Ranvier, clustering of myelin segments, abnormal lipid-filled cells, frequent degenerating cells, and rare distorted myelin profiles. In contrast, qk has abnormally numerous oligodendrocytes, frequent nodes of Ranvier, no obvious myelin clustering, no lipid-filled cells, rare degenerating cells, and frequent abnormal or distorted myelin profiles. jp and jpmsd are quantitatively different, but qualitatively similar. Since its origin, the jpmsd disease has inadvertently been ameliorated by transferring the mutation to a different background. Persistent differences in the remainder of the genome might account for all remaining apparent differences between jp and jpmsd. In contrast, qk is totally dissimilar in morphology and presumably in pathophysiology.