Summary
We describe a number of biochemical and pathological findings in a neurological syndrome which resulted from a mutation in the congenic resistant strain, B10.C(47N). The mutation, designated with the symbol msd, is sex-linked, recessive, and causes tremor, repeated seizures, and death of affected males at about 18–23 days of postnatal age. The earliest detectable clinical signs appear around 10 days of age. The CNS is markedly deficient in myelin. The white matter fiber tracts appear essentially as “negative images”. In contrast, the peripheral nerves are myelinated.
Among quantitative differences in lipid composition of the CNS between normal and mutant mice, major deficiencies involve cholesterol and galactolipids, i.e., cerebrosides and sulfatides, but not gangliosides. Quantitative and qualitative abnormalities of cerebrosides, sulfatides, and sphingomyelin are detectable chromatographically. Both cerebroside spots are lacking, sulfatides are either absent or greatly diminished, and only the lower sphingomyelin band is present. A major difference between mutant and control brains involves the ratio of total saturated to unsaturated fatty acids which is significantly higher in mutant than control mice, an indication that the mutant brain is less able to retain unsaturates. The situation with respect to dimethylacetals of plasmalogens has not yet been resolved.
Although msd is similar to jp (jimpy) genetically and biochemically, tests for allelism and linkage to determine the position of the two genes relative to one another are still inconclusive. Therefore, it appears at present more likely that the two genes are different and non-allelic.
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The deviant mouse was discovered by Mrs. Helen P. Bunker in the mouse colonies of Dr. George D. Snell. The mutation is maintained in the laboratory of the late Dr. Margaret M. Dickie. This article is dedicated to Dr. Dickie in professional gratitude.
This investigation was supported in part by Public Health Service research grant NB 06448 from the National Institute of Neurological Diseases and Stroke, a grant from the National Foundation for Neuromuscular Diseases, Inc., a grant from the United Medical Research Foundation of North Carolina, and a grant from the Southwaite Foundation.
The principles of laboratory animal care as promulgated by the National Society for Medical Research are observed in this Laboratory.
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Meier, H., MacPike, A.D. A neurological mutation (msd) of the mouse causing a deficiency of myelin synthesis. Exp Brain Res 10, 512–525 (1970). https://doi.org/10.1007/BF00234267
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DOI: https://doi.org/10.1007/BF00234267