engleski

Different ganglioside expression in tissues of mice homozygous (-/-)and heterozygous (+/-) for the TNF receptor p55 knock out

This study presents a comparative ionvestigation of gangliosides from lymphoid (spleen and thymus) and other tissues (lung, brain, muscle, liver) of mice lacking the tumor necrosis factor receptor 1 (TNFRp55). Gangliosides from C57BL/6 mice homozygous (-/-) and heterozygous (+/-) for the TNFRp55 knockout were isolated according to standard procedures. Quantitative and qualitative difference of both strains were revealed by means of DMB-derivatives of sialic acids from gangliosides and TLC-immunostaining with a panel of ganglioside specific antibodies (Muthing, 1996, 1998). This approach showed homologies but also quantitative and qualitative differences in the expression of GM3(Neu5Ac), GM3(Neu5GC), GM1b-type and nelacto series gangliosides in some organs of homo- and heterozygous mice. Sialic acide profiles showed strong increase of the apsolute amount of lipid-bound sialic acids (Neu5Ac+Neu5Gc) in the lungs and thymus of homozygous mice (1.41 and 0.3 ng/mg wet weight, respectively) compared to heterozygous animals (7.18 and 2.05 ng/mg wet weight, respectively) and considerable difference of Neu5Ac/Neu5Gc ratios in lung, muscle, spleen and thymus as well. Concerning the ganglioside patterns, GM3 (Neu5Ac) was ten times and GM3(Neu5Gc) seven times more abundant in lungs of heterozygous animals. Enhanced expression of GM1b-type gangliosides (GM1b and GalNAc-GM1b) was also found in the lungs, spleen and thymus of heterozygous (control) mice. On the other hand, neolacto-series gangliosides were more abundant inthe lungs, brain and muscle of the homozygous mice. The expression in liver, spleen and thymus was similar in the both groups of mice. This study provides in vivo evidence that TNF signaling via the TNFRp55 is involved in the acquisition of dictinct ganglioside profiles in different mouse organs. TNFRp55 signaling seems to be especially important for the activation of the GM1b type ganglioside biosynthetic pathway which is a unique characteristic of mouse lymphoid tissue.

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