Expression of Neutral Glycosphingolipids in the Brain and Spleen of Mice Lacking TNF Receptor 1

Abstract

We investigated the expression of neutral glycosphingolipids (GSLs) in the brain and spleen of mice lacking the gene for the tumor necrosis factor‐α receptor p55 (TNFR1). Neutral GSLs of the ganglio‐, globo‐, and neolacto‐series were determined in the tissues of homozygous (TNFR1 −/−) and control heterozygous (TNFR1 +/−) animals by high performance thin layer chromatography (HPTLC) overlay immunostaining with specific antibodies. The spleen of homozygous TNFR1 knockout mice lacked glucosylceramide substituted with palmitic acid, GlcCer(C16), and showed severe reduction in the expression of GlcCer(C24). In addition, gangliotetraosylceramide substituted with palmitic acid, Gg4Cer(C16), and globotetraosylceramide, Gb4Cer, were down‐regulated in the TNFR1 −/− spleen in comparison with the heterozygous control. The brain of both groups of animals (TNFR1 −/− and TNFR1 +/−) did not express detectable levels of Gg4Cer, Gb5Cer and Gb4Cer, but the brain of TNFR1 knockout mice expressed abundant globotriaosylceramide, Gb3Cer, compared to no expression in control heterozygous mice. nLcCer(C24) had slightly higher (1.4 fold) expression in the brain of TNFR1 −/− mice compared with the control animals. This study provides in vivo evidence that TNF signaling via the TNFR1 is involved in the acquisition of a divergent GSL assembly in the brain, an immunologically privileged organ, and the spleen, typical secondary lymphoid organ.