Growth retardation and early death of beta-1,4-galactosyltransferase knockout mice with augmented proliferation and abnormal differentiation of epithelial cells.
Carbohydrate chains on a glycoprotein are important not only for protein conformation, transport and stability, but also for cell-cell and cell-matrix interactions. UDP-Gal:N-acetylglucosamine beta-1,4-galactosyltransferase (GalT) (EC 2.4.1.38) is the enzyme which transfers galactose (Gal) to the terminal N-acetylglucosamine (GlcNAc) of complex-type N-glycans in the Golgi apparatus. In addition, it has also been suggested that this enzyme is involved directly in cell-cell interactions during fertilization and early embryogenesis through a subpopulation of this enzyme distributed on the cell surface. In this study, GalT-deficient mice were produced by gene targeting in order to examine the pathological effects of the deficiency. GalT-deficient mice were born normally and were fertile, but they exhibited growth retardation and semi-lethality. Epithelial cell proliferation of the skin and small intestine was enhanced, and cell differentiation in intestinal villi was abnormal. These observations suggest that GalT plays critical roles in the regulation of proliferation and differentiation of epithelial cells after birth, although this enzyme is dispensable during embryonic development.
Asano
M
M
Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Minato-ku, Japan.
Furukawa
K
K
Kido
M
M
Matsumoto
S
S
Umesaki
Y
Y
Kochibe
N
N
Iwakura
Y
Y
D000818:Animals; D002239:Carbohydrate Metabolism, Inborn Errors / Q000201:enzymology; D002240:Carbohydrate Sequence; D002454:Cell Differentiation; D002455:Cell Division; D004848:Epithelium / Q000473:pathology; D005260:Female; D005690:Galactose / Q000378:metabolism; D006130:Growth Disorders / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D007421:Intestine, Small / Q000201:enzymology / Q000473:pathology*; D043322:Lactase; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008871:Microvilli; D008969:Molecular Sequence Data; D009237:N-Acetyllactosamine Synthase / Q000172:deficiency* / Q000235:genetics; D012867:Skin / Q000473:pathology*; D013394:Sucrase-Isomaltase Complex / Q000378:metabolism; D000520:alpha-Glucosidases / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism; D006022:beta-N-Acetylglucosaminylglycopeptide beta-1,4-Galactosyltransferase / Q000172:deficiency* / Q000235:genetics
D006022:beta-N-Acetylglucosaminylglycopeptide beta-1,4-Galactosyltransferase; D009237:N-Acetyllactosamine Synthase; D013394:Sucrase-Isomaltase Complex; D043322:Lactase; D000520:alpha-Glucosidases; D001616:beta-Galactosidase; D005690:Galactose