Remodeling of mouse milk glycoconjugates by transgenic expression of a human glycosyltransferase.
The mammary gland is a unique biosynthetic tissue that produces a variety of species-specific glycoconjugates, but the factors regulating the production of specific glycoconjugates are not well understood. To explore the underlying regulation, a fusion gene containing a cDNA encoding the human alpha 1,2-fucosyltransferase (alpha 1,2FT), which generates the H-blood group antigen, flanked by the murine whey acidic protein promoter and a polyadenylation signal, was introduced into mice. Milk samples from transgenic animals contained soluble forms of the alpha 1,2FT, as revealed by Western blots of milk samples using an anti-alpha 1,2FT antiserum and by the demonstration of alpha 1,2FT enzyme activity. Milk from transgenic animals also contained large quantities of 2'-fucosyllactose (Fuc alpha 1-2Gal beta 1-4Glc) and modified glycoproteins containing the H-antigen, whereas milk from control animals lacked these glycoconjugates. Expression levels of 2'-fucosyllactose were high in most animals and represented 1/3 to nearly 1/2 of the total milk oligosaccharides. These results demonstrate that heterologous transgenic expression of a glycosyltransferase can result in the expression of both the transgene and its secondary gene products and that the structures of milk oligosaccharides can be remodeled depending on expression of the appropriate enzyme. Furthermore, these results suggest that the lactating mammary gland may be a unique biosynthetic reactor for the production of biologically active oligosaccharides and glycoconjugates.
D000017:ABO Blood-Group System / Q000032:analysis; D000818:Animals; D005647:Fucosyltransferases / Q000235:genetics; D006001:Glycoconjugates / Q000096:biosynthesis* / Q000235:genetics; D016695:Glycosyltransferases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008892:Milk / Q000737:chemistry*; D009844:Oligosaccharides / Q000032:analysis; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D000017:ABO Blood-Group System; D005647:Fucosyltransferases; D006001:Glycoconjugates; D016695:Glycosyltransferases; D009844:Oligosaccharides; D000097631:Galactoside 2-alpha-L-fucosyltransferase