The levels of myelin basic protein, proteolipid protein, and 2',3'-cyclic nucleotide 3'-phosphohydrolase (EC 3.1.4.37) in cerebral hemispheres of wild-type, heterozygous jp/+, and hemizygous jp/Y mice of different ages were determined by radioimmunoassay and immunoblotting. In jp/Y brain the level of myelin basic protein was 8% that of wild-type at all ages. All forms of the protein were reduced although the 21.5K Mr form was relatively spared at early ages compared to the 18.5K, 17K, and 14K Mr forms. The level of 2',3'-cyclic nucleotide 3'-phosphohydrolase was 8% that of wild-type at all ages, and proteolipid protein was undetectable at any age. These results are consistent with the hypothesis that the jimpy mutation blocks myelin morphogenesis subsequent to incorporation of 21.5K Mr myelin basic protein but prior to incorporation of proteolipid protein. In jp/+ brain the levels of the three proteins were reduced commensurately to 60-70% those of wild-type. The deficit was apparent as early as 10 days after birth and remained proportionately constant throughout development. These results suggest that in jp/+ mice, X-chromosome inactivation produces a mosaic population of functionally wild-type and functionally jimpy oligodendrocytes. The former elaborate normal amounts of myelin but do not completely compensate for the myelin deficit due to the latter.

A new recessive mutation, spasmodic (spd), producing behavior that mimics that of the neurological mutation spastic (spa) with rapid tremors, stiff posture, and difficulty in righting, arose spontaneously in strain A/HeJ at the Jackson Laboratory in 1979. It is not an allele of spa and linkage tests show that this mutation is located close to vestigial tail (vt) near the center of chromosome 11. Additional genetic tests show that it is not an allele of trembler (Tr), shaker-2 (sh-2), nor vibrator (vb), all neurological mutations located in the same region of chromosome 11. No differences were observed in the levels of the major CNS and PNS myelin proteins or lipids of spd/spd mice versus littermate controls, suggesting that, unlike several closely linked mutations, the spd mutation does not affect myelination. Pharmacological studies reported here show that aminooxyacetic acid improves the behavioral abnormalities of affected spd/spd mice in the same way it improves the behavior of affected spa/spa mice. However, unlike the spa/spa mice, there are no changes in the postsynaptic receptors for glycine, GABA, or benzodiazepines in spd/spd mice.

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The lipids of white matter and peripheral nerve from mutant mice with known myelin deficiencies were analyzed by one- and two-dimensional high-performance thin-layer chromatography and quantitated by densitometry. In optic nerve, the mutants jp/Y, jp^msd/Y, qk/qk, shi/shi and shi^mld/shi^mld, which have severe central nervous system (CNS) myelin deficiency, had a common pattern of lipid loss: cerebrosides and sulfatides (hydroxy and nonhydroxy forms) were generally reduced by 70–95% or more; most phospholipids were diminished by 15–55%, and cholesterol was reduced by 35–60%. Only in the CNS of jp/Y and jp^msd/Y did cholesterol ester accumulate. In peripheral nerve, the lipid composition varied markedly among these mutants. In jp/Y there was no change, while in jp^msd/Y there was a 5–15% loss among the phospholipids and cholesterol. Homozygous qk had reductions of 75–85% in the nonhydroxy forms of cerebroside and sulfatide, a 130% increase in hydroxy sulfatide, and a 55% loss of sphingomyelin. In shi/shi and shi^mld/shi^mld homozygotes, the glycolipids were altered by ± 20%, most phospholipids and cholesterol were reduced by 5–15%, and sphingomyelin was reduced by 40%. Tr and Tr^J showed 35–90% reductions in most lipid classes of the peripheral nervous system; CNS lipid composition was normal. Homozygous twi had a uniform loss of most lipid classes in both optic (generally 10–20%) and trigeminal nerves (generally 40–55%); cerebrosides did not accumulate in these tissues, dy/dy had a 10–20% reduction of cerebrosides in trigeminal nerve trunk. The CNS of dy homozygotes had 10–35% increases in specific classes of glycolipids and phospholipids, and in cholesterol. None of the mutants showed detectable levels of lysophospholipids or other unusual lipid species. The fractions of ethanolamine and choline phosphatides in the plasmalogen form were close to normal in all mutants.