Deficiency of reproductive tract alpha(1,2)fucosylated glycans and normal fertility in mice with targeted deletions of the FUT1 or FUT2 alpha(1,2)fucosyltransferase locus.
The fucose alpha(1-->2) galactose beta 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. Fucalpha(1-->2)Galbeta 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 Fucalpha(1-->2)Galbeta 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:beta(1-->4)-D-galactosyl-R 2-alpha-L-fucosyltransferase enzymes (EC 2.4.1.69) responsible for Fucalpha(1-->2)Galbeta synthesis and expression. FUT1 null mice and FUT2 null mice develop normally and exhibit no gross phenotypic abnormalities. The Fucalpha(1-->2)Galbeta 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 Fucalpha(1-->2)Galbeta 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.
Domino
S E
SE
Department of Obstetrics and Gynecology, 6428 Medical Science Bldg. 1, The University of Michigan Medical School, 1150 West Medical Center Dr., Ann Arbor, MI 48109, USA. sedomino@med.umich.edu
Zhang
L
L
Gillespie
P J
PJ
Saunders
T L
TL
Lowe
J B
JB
D000483:Alleles; D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D015139:Blotting, Southern; D004622:Embryo, Mammalian / Q000166:cytology; D004822:Epididymis / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000235:genetics* / Q000502:physiology; D005647:Fucosyltransferases / Q000235:genetics* / Q000502:physiology; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D037102:Lectins / Q000378:metabolism; D008297:Male; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D016366:Open Reading Frames; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011134:Polysaccharides / Q000096:biosynthesis*; D013234:Stem Cells / Q000378:metabolism; D014599:Uterus / Q000378:metabolism; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D005647:Fucosyltransferases; D037102:Lectins; D011134:Polysaccharides; D000097631:Galactoside 2-alpha-L-fucosyltransferase