Genetic control of ganglioside biosynthesis in mice.

The enzymatic basis for the differences in hepatic ganglioside patterns in the mouse strains C57Bl/6 and Swiss White (SW) was investigated. SW has a "Swiss-type" ganglioside profile, expressing GM1- and GD1a- in addition to GM2- as major hepatic gangliosides, whereas C57Bl/6 shows a "GM2-type" profile, expressing only GM2- as the major hepatic ganglioside. The enzyme UDP-galactose:GM2 ganglioside galactosyltransferase (GM2-GalT), which catalyzes the synthesis of GM1 ganglioside, showed a four- to fivefold elevation in intact and solubilized liver Golgi membrane fractions of the SW strain compared to C57Bl/6. Crosses between C57Bl/6 and SW produced an F1 generation with a hepatic ganglioside and enzymatic phenotype intermediate between those of the two parental strains. All three genotypic groups show two forms of the Golgi apparatus enzyme with isoelectric points of 6.5-6.8 and 8.3-9.0. The simplest mode of action of genes which control the enzymatic phenotype that would be consistent with these findings are one or two structural genes or one or two cis-regulatory genes affecting the rate of enzyme synthesis.