engleski

Developmental patterns of ganglioside expression in developing mouse brain

Gangliosides are predominant sialogycoconjugates in vertebrate nervous system. The most abundant structures in adult and fetal brain are GM1, GD1a, GD1b and GT1a. Their share same core structure consisting of ceramide lipid and neutral tetrasaccharide core (Gal b3 GalNAc b4 Gal b4 Glc) and veried in number and position of sialic acid. Neurobiological role for these major structures has not been defined. Recently developed knockout mice line of b1,4 GalNAc-T gene lacking all complex ganglio-series gangliosides showed decreased central myelination, axonal degeneration in central and peripheral nervous system, and demyelination in peripheral nerves. These results are in agreement with observation that mice lacking myelin-associated glycoprotein (MAG), known as in vitro receptor for GD1a and GT1b, show similar pathological features suggesting role of this structures in myelination. More elaborate study of distribution and function of major gangliosides in developing and adult brain was obstructed by lack of high-affinity IgG antibodies due to conservation of this molecules across mammalian and avian species. Knockout mice for b1,4 GalNAc-T gene are immunologically naďve to complex gangliosides and give robust respond upon immunization. We were able to develop high–affinity IgG antibodies against all four major brain gangliosides: GM1, GD1a, Gd1b and GT1a. Study of mice brain shows developmentally regulated pattern of expression different for each tested antibody giving insight in different metabolic regulation of glycosphingolipid synthesis for different brain structures.

gangliosides; development

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