Abnormalities caused by carbohydrate alterations in Ibeta6-N-acetylglucosaminyltransferase-deficient mice

Guo-Yun Chen; Hisako Muramatsu; Mineo Kondo; Nobuyuki Kurosawa; Yozo Miyake; Naoki Takeda; Takashi Muramatsu

doi:10.1128/MCB.25.17.7828-7838.2005

Abnormalities caused by carbohydrate alterations in Ibeta6-N-acetylglucosaminyltransferase-deficient mice

Mol Cell Biol. 2005 Sep;25(17):7828-38. doi: 10.1128/MCB.25.17.7828-7838.2005.

Authors

Guo-Yun Chen¹, Hisako Muramatsu, Mineo Kondo, Nobuyuki Kurosawa, Yozo Miyake, Naoki Takeda, Takashi Muramatsu

Affiliation

¹ Department of Biochemistry, Nagoya University School of Medicine, Japan.

Abstract

Ibeta6-N-acetylglucosaminyltransferase (IGnT) catalyzes the branching of poly-N-acetyllactosamine carbohydrate chains. In both humans and mice, three spliced forms of IGnT have been identified, and a common exon is present in all of them. We generated mice deficient in the common exon to understand the physiological function of poly-N-acetyllactosamine branching. IGnT activity was abolished in the stomach, kidney, bone marrow, and cerebellum of the deficient mice, while a low level of the activity persisted in the small intestine. Immunohistochemical analysis confirmed the loss of I antigen from the lung, stomach, and kidney. The deficient mice had reduced spontaneous locomotive activity. The number of peripheral blood lymphocytes was also reduced and renal function decreased in the deficient mice. Furthermore, in aged mice, vacuolization occurred in the kidney, and epidermoid cysts were frequently formed. However, cataracts did not develop earlier in the deficient mice. Decreased levels of lysosomal proteins, LAMP-2 and synaptotagmin VII, were found in the kidney of the deficient mice and correlated with renal abnormalities.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, CD / metabolism
Calcium-Binding Proteins / metabolism
Carbohydrate Metabolism*
Cataract / enzymology
Cataract / genetics
Epidermal Cyst / enzymology
Epidermal Cyst / genetics
Epidermal Cyst / pathology
Gene Deletion
Intracellular Membranes / enzymology
Kidney / abnormalities*
Kidney / enzymology
Kidney / metabolism
Kidney / pathology
Lymphocyte Count
Lymphocytes / cytology
Lysosomal Membrane Proteins
Lysosomal-Associated Membrane Protein 1
Lysosomes / enzymology
Lysosomes / genetics
Membrane Glycoproteins / metabolism
Mice
Mice, Knockout
Motor Activity
N-Acetylglucosaminyltransferases / deficiency*
N-Acetylglucosaminyltransferases / genetics
N-Acetylglucosaminyltransferases / metabolism*
Nerve Tissue Proteins / metabolism
Protein Binding
Synaptotagmin II
Synaptotagmins
Time Factors

Substances

Antigens, CD
Calcium-Binding Proteins
Lamp1 protein, mouse
Lysosomal-Associated Membrane Protein 1
Lysosomal Membrane Proteins
Membrane Glycoproteins
Nerve Tissue Proteins
Synaptotagmin II
Syt2 protein, mouse
Syt7 protein, mouse
Synaptotagmins
N-acetylglucosaminyltransferase IGnT
N-Acetylglucosaminyltransferases