Oocyte Galα1,3Gal Epitopes Implicated in Sperm Adhesion to the Zona Pellucida Glycoprotein ZP3 Are Not Required for Fertilization in the Mouse (*)

  1. Aron D. Thall(1),
  2. Petr Malý(2) and
  3. John B. Lowe(1)(2)(§)
  1. From the (1) Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109 and the
  2. (2) Howard Hughes Medical Institute, Ann Arbor, Michigan 48109-0650

    Abstract

    The Galα1Graphic3Gal structure is displayed on the zona pellucida glycoprotein ZP3 on murine oocytes. This trisaccharide has been implicated in sperm-zona pellucida adhesive events thought to be essential to fertilization in the mouse. To determine directly if this molecule is required for fertilization, we have generated mice that are deficient in a gene (α1,3GT) encoding the UDP-Gal:β-D-Gal-α1Graphic3Gal-galactosyltransferase enzyme responsible for Galα1Graphic3Gal synthesis and expression. These mice develop normally and exhibit no gross phenotypic abnormalities. The Galα1Graphic3Gal epitope is absent from the vascular endothelium and other tissues in α1,3GT (−/−) adult mice. By contrast, α1,3GT (−/−) mice, like humans, develop naturally occurring anti-α-galactoside antibodies normally absent in wild type mice. Female α1,3GT (−/−) mice yield oocytes that are devoid of the Galα1Graphic3Gal epitope; however, these mice are fully fertile. These observations indicate that the Galα1Graphic3Gal moiety is not essential to sperm-oocyte interactions leading to fertilization or to essentially normal development. They further suggest that α1,3GT (−/−) mice will find utility for exploring approaches to diminish anti-Gal-dependent hyperacute xenograft rejection, which presents a major barrier to the use of porcine and other non-primate organs for xenotransplantation in humans.

    Footnotes

    • § Associate Investigator of the Howard Hughes Medical Institute.

    • * The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • 1 The abbreviations used are:

      α1,3GT

      UDP-Gal:β-D-Gal-α1Graphic3Gal-galactosyltransferase

      ES

      embryonic stem cell(s)

      BSA

      bovine serum albumin

      PBS

      phosphate-buffered saline

      FITC

      fluorescein isothiocyanate

      BSIB4

      B. simplicifolia isolectin B4.

      • Received June 28, 1995.
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