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Glycobiology Advance Access originally published online on April 2, 2003
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Glycobiology, 2003, Vol. 13, No. 8 591-600
© 2003 Oxford University Press

Biologic contribution of P1 promoter–mediated expression of ST6Gal I sialyltransferase

Michelle M. Appenheimer6, Ruea-Yea Huang6, E.V. Chandrasekaran7, Martin Dalziel1,6, Yi Ping Hu2,6, Paul D. Soloway3,6, Sherry A. Wuensch4,6, Khushi L. Matta7 and Joseph T.Y. Lau5,6

6 The Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263
7 Department of Molecular and Cellular Biophysics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263

Received on January 27, 2003; revised on March 5, 2003; accepted on March 5, 2003

The synthesis of the common and well-documented Sia{alpha}2,6 to Galß1,4GlcNAc structure (Sia6LacNAc) is principally mediated by the sialyltransferase ST6Gal I, which is particularly highly expressed in liver, lactating mammary gland, intestinal epithelia of newborn animals, and B cells. Multiple independent promoters govern the expression of Siat1, the ST6Gal I gene. In liver, elevation of hepatic and serum ST6Gal is part of the acute phase reaction, the hepatic response to systemic trauma, and is governed by the inducible, liver-specific promoter-regulatory region, P1. A constitutive and nontissue-specific promoter, P3, mediates low-level, basal hepatic Siat1 transcription. We generated a mouse specifically unable to use the transcriptional initiation site uniquely used in P1-mediated ST6Gal I expression. These animals, Siat1{Delta}P1, are viable and display reduced ST6Gal I mRNA in liver with concomitantly reduced sialyltransferase activities in liver and in serum. Siat1{Delta}P1 animals are unable to elevate hepatic Siat1 mRNA as part of the inflammatory response induced by turpentine. Surprisingly, serum glycoprotein components exhibit normal extent of sialylation, with no noticeable difference in binding to SNA, the {alpha}2,6-sialyl-specific lectin. Siat1{Delta}P1 animals also exhibit an outwardly normal B cell response. On intraperitoneal challenge with the pathogen Salmonella typhimurium, a significantly greater accumulation of neutrophils within the peritoneal space was observed in Siat1{Delta}P1 animals compared to wild-type mice. Siat1{Delta}P1 mice also exhibit a greater bacterial burden in liver and spleen, accompanied by more pronounced spleno-/hepatomegaly and greater leukocyte infiltration into affected organs than their wild-type counterparts.

1 Present address: Centre de Biophysique Moleculaire, Rue Charlee Sadron (Bat B), 45071 Orleans, Cedex 07 France.

2 Present address: Dept of Cell Biology, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, China.

3 Present address: Division of Nutritional Sciences, Cornell University, 108 Savage Hall, Ithaca, NY 14853.

4 Present address: Davis H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY 14642.

5 To whom correspondence should be addressed; e-mail: joseph.lau{at}roswellpark.org


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