Genetic Regulation of GM4(NeuAc) Expression in Mouse Erythrocytes1

Abstract

The polymorphic expression of GM4(NeuAc), GM3(NeuGc), GM2(NeuGc), and GM1(NeuGc) was found in erythrocytes of inbred strains of mice [Nakamura, K. et al. (1988) J. Biochem. 103, 201-208]. In this paper, we report the results of genetic analysis of the expression of GM4(NeuAc) and GM2(NeuGc). Ganglioside analysis of the progeny obtained on mating between BALB/c mice [GM4 (+)] and WHT/Ht or C57BL/6 mice [both GM4 (-)] indicated that the expression of GM4(NeuAc) is an autosomal dominant trait, and that WHT/Ht and C57BL/6 mice carry a defect on a single autosomal gene. We named this gene Gsl-4. On quantitative determination of galactosylceramide (GalCer), which is the biosynthetic precursor of GM4(NeuAc), the content of GalCer was found to be quite low in WHT/Ht erythrocytes, compared with in BALB/c erythrocytes. On analysis of GM4(NeuAc) and GalCer in 92 backcross mice produced on mating between BALB/c and WHT/Ht mice, it was found that 45 GM4(+) mice apparently expressed a detectable amount of GalCer and that 47 GM4(-) mice expressed an almost undetectable amount of GalCer. These results suggest that Gsl-4 controls the expression of GM4(NeuAc) by regulating the content of GalCer. Linkage analysis of Gsl-4 and the gene controlling GM2(NeuGc) in erythrocytes indicated that the two genes are not genetically linked. Comparison of the ganglioside expression in liver and erythrocytes of the same backcross mice suggested that the gene controlling GM2(NeuGc) expression in the liver (Ggm-2) is also responsible for the expression of GM2(NeuGc) in erythrocytes.