Biochemical Abnormalities in Spinal Cord Myelin and CNS Homogenates in Heterozygotes Affected by the Shiverer Mutation

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Abstract
Myelin was purified from the spinal cords of normal mice and mice heterozygous for the shiverer mutation, and measurements were made of the major myelin proteins and lipids and the specific activities of 3 myelin-associated enzymes. The myelin purified from the spinal cords of the heterozygotes (shi/+) was deficient by 30-40% in yield and had an apparently unique composition. When compared with normal mouse spinal cord myelin, there were more high-MW protein, less myelin basic protein, a higher protein-to-lipid ratio, and higher specific activities of 2'',3''-cyclic nucleotide-3''-phosphohydrolase (EC 3.1.4.37) and carbonic anhydrase (EC 4.2.1.1) in the myelin purified from the shi/+ animals. These abnormalities were reflected in the composition of shi/+ whole spinal cord, where the protein-to-lipid ratio was intermediate between the respective values for +/+ and shi/shi spinal cords. Whole brains from shi/+ mice showed deficiencies in galactocerebroside and galactocerebroside sulfate and an increase in total phospholipid, and the lipid composition in the brains of the shi/shi mice was similar to that reported for another dysmyelinating mutant, quaking. The 1st values for the lipids in normal mouse spinal cord myelin are provided and show that heterozygotes are affected by the shiverer mutation. The observations imply that there can be considerable deviation from the normal CNS myelin content and composition without apparent qualitative morphologial abnormalities or loss of function, and that the amount of myelin basic protein available during myelination may influence the incorporation of other constituents into the myelin membranes. This is also the 1st report of enrichment in pure normal myelin, over normal spinal cord homogenates, of the enzymes carbonic anhydrase and 5''-nucleotidase (EC 3.1.3.5).