Advertisement

Glycoconjugates in Human and Transgenic Animal Milk

  • B. Kelder
  • R. Erney
  • John Kopchick
  • Richard Cummings
  • Pedro Prieto
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 501)

Abstract

Human milk samples contain a particularly rich collection of oligosaccharides compared with other milk samples. The synthesis of these molecules should depend on the expression of glycosyltransferases and the presence of sugar nucleotides in lactating mammary glands. We set out to produce transgenic animals expressing glycosyltransferases during lactation with the purpose of exploring the following issues: a) Is it possible to synthesize human milk oligosaccharides in lactating mammary glands of nonhuman animals?, b) Is it possible to express during lactation homologous, tissue specific glycosyltransferases that are not normally expressed in lactating mammary tissue?, and c) What is the effect of expressing a human glycosyltransferase in diffei -ent animal species? Simultaneously, we embarked on a research program to study short-chain neutral human milk oligosaccharides—no larger than hexasaccharidesto understand the natural variation of milk sugars and glycoproteins. The reagents and methods developed to study human milk oligosaccharides and glycoproteins were also applied to the study of milk from transgenic animals. Our results indicate that mice predictably express transgene-encoded glycosyltransferases and their secondary gene products, oligosaccharides and remodeled glycoproteins. This was true even when the transgene encoded a homologous galactosyltransferase. Also, it was possible to synthesize fucosylated glycoconjugates in mouse milk using two different fucosyltransferases, thus demonstrating that is feasible to emulate the synthesis occurring in the human lactating mammary gland. Experiments with transgenic rabbits yielded different phenotypes, some of them unexpected. Taken together, our results answer the questions stated above but open even more intriguing areas of inquiry.

Keywords

Milk Sample Human Milk Transgenic Animal Milk Oligosaccharide Lactate Mouse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Reference

  1. Cho SK, Cummings RD. A soluble form of a1,3-galactosyltransferase functions within cells to galactosylate glycoproteins. J Biol Chem 1997;272:13622–13628.PubMedCrossRefGoogle Scholar
  2. Larsen RD, Rajan VP, Ruff MM, Kukowska-Latallo J, Cummings RD, Lowe JB. Isolation of a cDNA encoding a murine UDP-galactose:3-D-galactosyl-1,4-N-acetyl-D-glucosaminide a1,3galactosyltransferase: expression cloning by gene transfer. Proc Natl Acad Sci USA 1989;86:8227–8231.PubMedCrossRefGoogle Scholar
  3. Prieto PA, Mukerji P, Kelder B, Erney R, Gonzalez D, Yun JS, Smith DF, Moremen KW, Nardelli C, Pierce M, Li Y, Chen X, Wagner TE, Cummings RD, Kopchick J.I. Remodeling of mouse milk glycoconjugates by transgenic expression of a human glycoyltransferase. J Biol Chem 1995;270:29515–29519.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • B. Kelder
    • 1
  • R. Erney
    • 2
  • John Kopchick
    • 1
  • Richard Cummings
    • 3
  • Pedro Prieto
    • 2
  1. 1.Edison Biotechnology Institute and Dept. of Biomedical Sciences Ohio UniversityAthens
  2. 2.Abbott LaboratoriesColumbus
  3. 3.University of Oklahoma Dept. of Biochemistry and Molecular Biology Health Sciences CenterOklahoma City

Personalised recommendations