Genetic regulation of GM2 (NeuGc) expression in liver of mouse.

GM2 containing NeuGc was a major ganglioside in mouse liver of inbred strains such as DBA/2, BALB/c, C57BL/10 and C3H/He, which are commonly used for biochemical and immunological studies. On the other hand, the liver of WHT/Ht, an inbred strain, contained GM3 (NeuGc) as a major ganglioside and lacked GM2 (NeuGc). We report here that the GM2 (NeuGc) expression was analyzed in the liver of the progeny between WHT/Ht and DBA/2 and the positive expression of GM2 (NeuGc) was proved to be a dominant trait regulated by an autosomal single gene. Moreover, the N-acetylgalactosaminyltransferase activity to convert GM3 (NeuGc) to GM2 (NeuGc) was measured in the liver microsomal fraction of WHT/Ht, BALB/c and their F1. F1 expressed almost half of the activity in BALB/c and WHT/Ht did not express a detectable amount of activity. The backcross of F1 to WHT/Ht segregated into two groups. One expressed both GM2 (NeuGc) and the transferase activity and the other expressed neither of them. There was no exceptional individual which was not grouped into either of these two groups. These results indicate that GM2 (NeuGc) expression is directly regulated by the N -acetylgalactosaminyltregated into two groups. One expressed both GM2 (NeuGc) and the transferase activity and the other expressed neither of them. There was no exceptional individual which was not grouped into either of these two groups. These results indicate that GM2 (NeuGc) expression is directly regulated by the N-acetylgalactosaminyltransferase activity, the expression of the enzyme activity is regulated by an autosomal single gene and WHT/Ht is a mutant of the recessive homozygote which cannot express the enzyme activity in its liver. WHT/Ht does not develop any neurological symptoms but grows and breeds well. The brain ganglioside composition was proved to be identical to those in BALB/c brain. The result suggests that WHT/Ht has N-acetylgalactosaminyltransferase to convert GM3 (NeuAc) to GM2 (NeuAc) in its brain. It is a subject for further study to elucidate what kind of defect is involved in the GM2 (NeuGc) biosynthesis of WHT/Ht liver.