Heterosis for brain cerebroside synthesis in mice

The (C57BL/6J X DBA/2J) F1 or B6D2F1 hybrid mice are known to exhibit a transitory hypermyelinating activity compared with their parental strains B6 and D2. These mice exhibit an elevated accumulation of cerebrosides in the brain which can be explained by an increase in their synthesis. Analysis of the two major cerebroside species indicated that the elevated content of total cerebrosides in the cerebellum and cerebrum of B6D2F1, as well as D2B6F1 hybrids, reflected an increased accumulation of the hydroxylated species. The UDP-galactose:ceramide galactosyltransferase (CgalT) activities in B6, D2 and hybrid mice were studied using as substrates alpha-hydroxy fatty acid (HFA)-containing ceramides or normal fatty acid (NFA)-containing ceramides (HFA- and NFA-CgalT activities, respectively). Both CgalT activities were found to be about 2 times higher in the cerebellum than in the cerebrum for all the strains studied. Before 20 days of age, the HFA-CgalT activities in B6D2F1, D2B6F1 and D2 mice were higher than in B6. However, at 20 days, there was no difference between B6 and D2 while the HFA-CgalT activity in the hybrids remained about 20% higher than in the parental strains. In contrast, no strain differences could be detected for the NFA-CgalT activity at all ages. The data suggest that the increased synthesis of brain cerebrosides in the B6D2F1 and D2B6F1 strains of mice could be largely accounted for by an increased HFA-CgalT activity.