title: Lysosomal di-N-acetylchitobiase-deficient mouse tissues accumulate Man2GlcNAc2 and Man3GlcNAc2.
abstract: Most lysosomal storage diseases are caused by defects in genes encoding for acidic hydrolases. Deficiency of an enzyme involved in the catabolic pathway of N-linked glycans leads to the accumulation of the respective substrate and consequently to the onset of a specific storage disorder. Di-N-acetylchitobiase and core specific α1-6mannosidase represent the only exception. In fact, to date no lysosomal disease has been correlated to the deficiency of these enzymes. We generated di-N-acetylchitobiase-deficient mice by gene targeting of the Ctbs gene in murine embryonic stem cells. Accumulation of Man2GlcNAc2 and Man3GlcNAc2 was evaluated in all analyzed tissues and the tetrasaccharide was detected in urines. Multilamellar inclusion bodies reminiscent of polar lipids were present in epithelia of a scattered subset of proximal tubules in the kidney. Less constantly, enlarged Kupffer cells were observed in liver, filled with phagocytic material resembling partly digested red blood cells. These findings confirm an important role for lysosomal di-N-acetylchitobiase in glycans degradation and suggest that its deficiency could be the cause of a not yet described lysosomal storage disease.
authors.affiliation: University of Perugia, D.S.E.E.A., Institute of Food Chemistry, Biochemistry, Physiology and Nutrition, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Persichetti
authors.forename: Katharina
authors.initials: K
authors.lastname: Klein
authors.forename: Silvia
authors.initials: S
authors.lastname: Paciotti
authors.forename: Karine
authors.initials: K
authors.lastname: Lecointe
authors.forename: Chiara
authors.initials: C
authors.lastname: Balducci
authors.forename: Sebastian
authors.initials: S
authors.lastname: Franken
authors.forename: Sandrine
authors.initials: S
authors.lastname: Duvet
authors.forename: Ulrich
authors.initials: U
authors.lastname: Matzner
authors.forename: Rita
authors.initials: R
authors.lastname: Roberti
authors.forename: Dieter
authors.initials: D
authors.lastname: Hartmann
authors.forename: Volkmar
authors.initials: V
authors.lastname: Gieselmann
authors.forename: Tommaso
authors.initials: T
authors.lastname: Beccari
mesh_terms: D000118:Acetylglucosaminidase / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004187:Disaccharides / Q000032:analysis / Q000378:metabolism*; D053595:Embryonic Stem Cells; D018390:Gene Targeting; D007687:Kidney Tubules, Proximal / Q000201:enzymology; D007728:Kupffer Cells / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D016464:Lysosomal Storage Diseases / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009844:Oligosaccharides / Q000378:metabolism / Q000652:urine; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014018:Tissue Distribution; D043323:alpha-Mannosidase / Q000032:analysis / Q000378:metabolism*; D001617:beta-Glucosidase / Q000032:analysis
chemical_list: D004187:Disaccharides; C503888:Man(3)GlcNAc(2); D009844:Oligosaccharides; C060051:mannosyl(2)-N-acetyl(2)-glucose; C530409:Ctbs protein, mouse; D001617:beta-Glucosidase; D043323:alpha-Mannosidase; D000118:Acetylglucosaminidase