Lysosomal di-N-acetylchitobiase-deficient mouse tissues accumulate Man2GlcNAc2 and Man3GlcNAc2

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• 作者：Emanuele Persichetti^a ; Katharina Klein^b ; Silvia Paciotti^a ; Karine Lecointe^c ; Chiara Balducci^a ; Sebastian Franken^b ; Sandrine Duvet^c ; Ulrich Matzner^b ; Rita Roberti^d ; Dieter Hartmann^e ; Volkmar Gieselmann^b ; Tommaso Beccari^a ; ^{tbeccari@unipg.it}
• 关键词：Lysosomal di-N-acetylchitobiase ; Lysosomal storage disease ; Knockout mouse ; N-linked glycan
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Basis of Disease
• 出版年：2012
• 期刊代码：19_09254439
• 类别：bio
• 出版时间：July, 2012
• 卷：1822
• 期：7
• 页码：1137-1146
• 文件大小：1493 K

摘要

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 伪1-6mannosidase 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.