Immunocytochemical investigations were performed on Jimpy and control mouse brains using three specific anti-myelin proteolipids antisera: immunoaffinity purified multivalent anti-(PLP + DM-20) proteolipid antibodies, anti-C-terminal hexapeptide 271-276 and anti-tridecapeptide 117-129 antisera. The results show that oligodendrocytes and myelin sheaths in normal mouse brain are labelled to the same extent by the three specific antisera; in contrast, in Jimpy brain these cellular structures are only stained by the multivalent antibodies and the site-specific, anti-tridecapeptide antiserum. The absence of labelling with C-terminal hexapeptide antiserum in mutant brain is interpreted as the result of either a large deletion or a point mutation producing a frameshift in the C-terminal part of the sequences of the proteolipids PLP and DM-20. Furthermore, we show that this mutation prevents the normal transport of proteolipid molecules through the Golgi apparatus. The existence of a minor, extra-Golgi apparatus metabolic route for proteolipids to myelin structures is also discussed.

—The brains of Jimpy and Quaking mice were compared with those of the corresponding normal controls during the course of development. The activity of 2′,3′‐cyclic nucleotide 3′‐phosphohydrolase (CNP) was found to be markedly reduced in the affected animals. The reduction in the Jimpy mice was greater than in the Quaking mice. The activity of CNP seems to be proportional to that of myelin in the mutant mice. A similar reduction was found in spinal cords of the mutant mice, but there was no difference in CNP activity between the sciatic nerves of the mutant mice and those of the corresponding normal controls.

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