The Association of the Galactosyl Diglycerides of Brain with Myelination: II. THE INABILITY OF THE MYELIN-DEFICIENT MUTANT, JIMPY MOUSE, TO SYNTHESIZE GALACTOSYL DIGLYCERIDES EFFECTIVELY

Abstract

Abstract The brain of the jimpy mouse, a mutant with a severe deficiency of myelin in the central nervous system, has little ability to synthesize galactosyl diglyceride. Lipase and α- and β-galactosidase activity in the brain of the jimpy were the same as in normal littermates. Thus the very low concentration of monogalactosyl diglyceride found in the brain of the jimpy (19 nmoles per g, wet wt) compared with the normal (438 nmoles per g, wet wt) must be attributed to low synthesis by a galactosyltransferase pathway rather than to overly active degradative enzymes. The galactosyltransferase involved in the synthesis of psychosine and cerebroside was also reduced in the jimpy brain. The small amount of monogalactosyl diglyceride that is found in the jimpy is restricted predominantly to the microsomal fraction, whereas normal littermates of identical age had monogalactosyl diglyceride in both myelin and microsomal fractions of brain. The jimpy mouse appears to be unable to transfer galactosyl diglyceride from microsomes (site of synthesis) to myelin (site of deposition). The relative inability of the jimpy mouse to make and to transfer galactosyl diglyceride to myelin correlates well with relative absence of myelin in the jimpy and supports the contention that the galactosyl diglycerides are associated with the process of myelination.