Deficiency of Reproductive Tract α(1,2)Fucosylated Glycans and Normal Fertility in Mice with Targeted Deletions of the FUT1 or FUT2 α(1,2)Fucosyltransferase Locus

Abstract

The fucose α(1→2) galactose β structure is expressed by uterine epithelial cells in the mouse and has been implicated in blastocyst adhesion events thought to be required for murine implantation. Fucα(1→2)Galβ moieties and cognate fucosyltransferases are also expressed by epithelial cells of the male reproductive tract and have been implicated in sperm maturation events that may contribute to fertilization. To determine directly if Fucα(1→2)Galβ moieties are required for fertility, we have generated strains of mice that are deficient in genes encoding FUT1 and FUT2, a pair of GDP-l-fucose:β(1→4)-d-galactosyl-R2-α-l-fucosyltransferase enzymes (EC 2.4.1.69) responsible for Fucα(1→2)Galβ synthesis and expression. FUT1 null mice and FUT2 null mice develop normally and exhibit no gross phenotypic abnormalities. The Fucα(1→2)Galβ epitope is absent from the uterine epithelia of FUT2 null mice and from the epithelia of the epididymis of FUT1 null mice. Fully normal fertility is observed in FUT1 null intercrosses and in FUT2 null intercrosses. These observations indicate that Fucα(1→2)Galβ moieties are not essential to blastocyst-uterine epithelial cell interactions required for implantation and are not required for sperm maturation events that permit fertilization and that neither the FUT loci nor their cognate fucosylated glycans are essential to normal development.

ACKNOWLEDGMENTS

This work was supported by a fellowship grant from the Reproductive Scientist Development Program and NIH K08 HD01195 (S.E.D), P01 CA71932 (J.B.L), University of Michigan Cancer Research Committee John S. and Suzanne C. Munn Endowed Research Fund (S.E.D.), and University of Michigan Phoenix Memorial Laboratory Michigan Memorial-Phoenix Project no. 856 (S.E.D.). J.B.L. is an Investigator of the Howard Hughes Medical Institute.

We are grateful to the University of Michigan Transgenic Animal Core (L. Samuelson, S. Camper, E. Hughes, M. Berand, and M. Van Keuren), DNA Sequencing Core (R. Lyons, S. Genik, and C. Esposito), DNA Synthesis Core (C. Wong), and Comprehensive Cancer Center Research Histology and Immunoperoxidase Laboratory (M. Rubin, M. LeBlanc, and N. McAnsh). We acknowledge R. Palmiter for plasmid pnlacF, T. Doetschman for mice transgenic for the neo gene, and J. Rossant and J. C. Roder for the R1 cell line made available through the Transgenic Animal Model Core.