Abnormalities caused by carbohydrate alterations in Ibeta6-N-acetylglucosaminyltransferase-deficient mice.
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.
Chen
Guo-Yun
GY
Department of Biochemistry, Nagoya University School of Medicine, Japan.
Muramatsu
Hisako
H
Kondo
Mineo
M
Kurosawa
Nobuyuki
N
Miyake
Yozo
Y
Takeda
Naoki
N
Muramatsu
Takashi
T
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002386:Cataract / Q000201:enzymology / Q000235:genetics; D004814:Epidermal Cyst / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D017353:Gene Deletion; D007425:Intracellular Membranes / Q000201:enzymology; D007668:Kidney / Q000002:abnormalities* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology; D052118:Lysosomal-Associated Membrane Protein 1; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000201:enzymology / Q000235:genetics; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D017351:N-Acetylglucosaminyltransferases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011485:Protein Binding; D050861:Synaptotagmin II; D050857:Synaptotagmins; D013997:Time Factors
D015703:Antigens, CD; D002135:Calcium-Binding Proteins; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D050861:Synaptotagmin II; C494263:Syt2 protein, mouse; C494303:Syt7 protein, mouse; D050857:Synaptotagmins; C106501:N-acetylglucosaminyltransferase IGnT; D017351:N-Acetylglucosaminyltransferases