Abnormal metabolism of 35SO4-sulfatide in jimpy brains expressed in brain organotypic cultures.

Cerebroside-sulfotransferase (CST), creatine-phosphokinase (CPK), and 3-hydroxy-3-methylglutaroyl CoA (HMG CoA) reductase activity, protein, and DNA content were measured in an easy-to-perform organotypic culture system of newborn normal and jimpy brains. The defective sulfatide synthesis which has been shown in vivo in jimpy brains could also be demonstrated in organ cultures of jimpy mice in the form of lowered CST activity in the homogenate as well as reduced 35SO4 incorporation into 35SO4-sulfatide. HMG CoA reductase was reduced to 60% of that found in 16-day-old normal cultures, similar to the findings in vivo. DNA of jimpy cultures was significantly lower than that in normal cultures, suggesting the possibility of an arrest in the differentiation or increased cellular death of presumptive oligodendrocytes, as was found in vivo. Organ cultures of jimpy mouse brain can serve as an appropriate model for further study of the primary defect in this animal mutant.