Kidney lipids in galactosylceramide synthase-deficient mice: absence of galactosylsulfatide and compensatory increase in more polar sulfoglycolipids 1

UDP-galactose:ceramide galactosyltransferase (CGT) catalyzes the final step in the synthesis of galactosyl- ceramide (GalCer). It has previously been shown that CGT- deficient mice do not synthesize GalCer and its sulfated de- rivative GalCer I 3 -sulfate (galactosylsulfatide, SM4s) but form myelin containing glucosylceramide (GlcCer) and sphin- gomyelin with 2-hydroxy fatty acids. Because relatively high concentrations of GalCer and SM4s are present also in mammalian kidney, we analyzed the composition of lipids in the kidney of Cgt 2 / 2 and, as a control, Cgt 1 / 2 and wild- type mice. The homozygous mutant mice lacked GalCer, galabiaosylceramide (Ga 2 Cer), and SM4s. Yet, they did not show any major morphological or functional defects in the kidney. A slight increase in GlcCer containing 4-hydroxy- sphinganine was evident among neutral glycolipids. Intrigu- ingly, more polar sulfoglycolipids, that is, lactosylceramide II 3 -sulfate (SM3) and gangliotetraosylceramide II 3 ,IV 3 - bis - sulfate (SB1a), were expressed at 2 to 3 times the normal levels in Cgt 2 / 2 mice, indicating upregulation of biosynthe- sis of SB1a from GlcCer via SM3. Given that SM4s is a ma- jor polar glycolipid constituting renal tubular membrane, the increase in SM3 and SB1a in the mice deficient in CGT and thus SM4s appears to be a compensatory process, which could partly restore kidney function in the knockout mice. —Tadano-Aritomi, K., T. Hikita, H. Fujimoto, K. Suzuki, K. Motegi, and I. Ishizuka. Kidney lipids in galactosylcera- mide synthase-deficient mice: absence of galactosylsulfatide and compensatory increase in more polar sulfoglycolipids. J. Lipid Res. 2000. 41: 1237-1243.