Neutral sphingomyelinase 1 deficiency in the mouse causes no lipid storage disease.
Sphingomyelin is a major lipid in the bilayer of subcellular membranes of eukaryotic cells. Different sphingomyelinases catalyze the initial step in the catabolism of sphingomyelin, the hydrolysis to phosphocholine and ceramide. Sphingomyelinases have been postulated to generate ceramide as a lipophilic second messenger in intracellular signaling pathways involved in cell proliferation, differentiation, or apoptosis. To elucidate the function of the first cloned Mg(2+)-dependent, neutral sphingomyelinase (nSMase 1) in sphingomyelin catabolism and its potential role in signaling processes in a genetic and molecular approach, we have generated an nSMase 1-null mutant mouse line by gene targeting. The nSMase 1-deficient mice show an inconspicuous phenotype and no accumulation or changed metabolism of sphingomyelin or other lipids, despite grossly reduced nSMase activity in all organs except brain. We also addressed the recent proposal that nSMase 1 possesses lysophospholipase C activity. The unaltered metabolism of lysophosphatidylcholine or lyso-platelet-activating factor excludes the proposed role of nSMase 1 as a lysophospholipase C.
Zumbansen
Markus
M
Laboratory of Molecular Neurosciences, Institute of Biochemistry, Faculty of Medicine, University of Cologne, Cologne, Germany.
Stoffel
Wilhelm
W
D000818:Animals; D003001:Cloning, Molecular; D005260:Female; D018390:Gene Targeting; D050356:Lipid Metabolism; D008052:Lipid Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009542:Niemann-Pick Diseases / Q000201:enzymology / Q000235:genetics; D010641:Phenotype; D013108:Sphingomyelin Phosphodiesterase / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
D013108:Sphingomyelin Phosphodiesterase