The distribution and biosynthesis of the myelin-galactolipids in the subcellular fractions of brains of quaking and normal mice during development.

Abstract

Abstract— The biosynthesis and accumulation of monogalactosyl diglyceride, galacto‐cerebrosides and sulfatides were studied in the brain of quaking mouse during myelination. The specific activity of monogalactosyl diglyceride synthesis of the mutant mouse was reduced to 50% of the control of the same age, comparable to the reduction in the biosynthesis of galactosylcerebrosides and sulfatides. The three galactolipids were largely associated with the myelin and microsomal fractions in the normal and quaking mice at the ages studied. Although the concentrations of microsomal galactolipids (expressed as nmol/g wet wt of brain) were lower in quaking mice than in the controls at all ages, the percentage of total brain monogalactosyl diglyceride recovered in the microsomes of the mutant mouse was always larger than in the microsomes of the controls. Between 16 and 41 days, the monogalactosyl diglyceride content of the control myelin increased 10‐fold, whereas the concentrations in the mutant increased only 2‐fold. In normal animals, the percentage of total myelin galactolipids in the ‘small myelin’ decreased over the age of 1841 days with concomitant increase in the ‘large myelin’. In contrast, in the mutant, large percentages of these compounds remained associated with the small myelin even at late periods of myelin development. These findings indicate that the slow rate of deposition of myelin in the brain of quaking mouse may be due to a defective transport mechanism of the galactolipids from the site of synthesis (microsomes) to the site of deposition (myelin), or to a defect in the mechanism of final myelin assembly, rather than to a lipid‐specific genetic error.