Glycobiology, 2001, Vol. 11, No. 2 165-174
© 2001 Oxford University Press
Ectopic expression of 
1,6 fucosyltransferase in mice causes steatosis in the liver and kidney accompanied by a modification of lysosomal acid lipase
3Department of Biochemistry, Osaka University Medical School, Osaka 565-0871, Japan, 4Department of Internal Medicine and Molecular Science, Osaka University Medical School, Osaka 565-0871, Japan, 5Osaka International University for Women, Osaka 570-0014, Japan, 6Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan, and 7Division of Human Genetics, Children’s Hospital Research Foundation, Cincinnati, OH 45229-3039, USA
The 
1,6 fucosyltransferase (1,6 FucT) catalyzes the transfer of a fucose from GDP-fucose to the innermost GlcNAc residue of N-linked glycans via an 1,6 linkage. 1,6 FucT was overexpressed in transgenic mice under the control of a combined cytomegalovirus and chicken ß-actin promoter. Histologically numerous small vacuoles, in which lipid droplets had accumulated, were observed in hepatocytes and proximal renal tubular cells. Electron microscopic studies showed that the lipid droplets were membrane-bound and apparently localized within the lysosomes. Cholesterol esters and triglycerides were significantly increased in liver and kidney of the transgenic mice. Liver lysosomal acid lipase (LAL) activity was significantly lower in the transgenic mice compared to the wild mice, whereas LAL protein level, which was detected immunochemically, was increased, indicating that the specific activity of LAL was much lower in the transgenic mice. In all of the transgenic and nontransgenic mice examined, the activity of liver LAL was negatively correlated with the level of 1,6 FucT activity. As evidenced by lectin and immunoblot analysis, LAL was found to be more fucosylated in the transgenic mice, suggesting that the aberrant fucosylation of LAL causes an accumulation of inactive LAL in the lysosomes. Such an accumulation of inactive LAL could be a likely cause for a steatosis in the lysosomes of the liver and kidney in the case of the 1,6 FucT transgenic mice.
1 These authors contributed equally to this work.
2 To whom correspondence should be addressed
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