Glycobiology Advance Access originally published online on October 23, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Glycobiology vol 14 no 2 pp. 169-175, 2004
© Oxford University Press 2004; all rights reserved.
LacZ expression in Fut2-LacZ reporter mice reveals estrogen-regulated endocervical glandular expression during estrous cycle, hormone replacement, and pregnancy
Department of Obstetrics and Gynecology, Cellular and Molecular Biology Program, 6428 Medical Science I Box 0617, University of Michigan Medical Center, Ann Arbor, MI 48109-0617, USA
Received on August 6, 2003; revised on October 3, 2003; accepted on October 6, 2003
 |
Abstract |
|---|
 Top Abstract IntroductionResultsDiscussionMaterials and methodsReferences |
|---|
The secretor gene (FUT2) encodes an
(1,2)fucosyltransferase (E.C. 2.4.1.69) that elaborates (1,2)fucose residues on mucosal epithelium and secreted mucins. Though uterine (1,2)fucosylated glycans have been proposed to be involved in embryo adhesion, mice with a homozygous null mutation of Fut2 displayed normal fertility. To help develop alternative hypotheses for function, the cell type and regulation of Fut2 expression during the estrous cycle, hormone replacement, and pregnancy was examined in Fut2-LacZ reporter mice containing targeted replacement of Fut2 with bacterial lacZ. LacZ expression in the reproductive tract of Fut2-LacZ mice is most prominent in the glandular epithelium of the endocervix during estrus and pregnancy. Nuclear LacZ expression identifies cell-specific expression of Fut2 in mucus-secreting cells of the endocervix, uterine glands, foveolar pit and chief cells of the stomach, and goblet cells of the colon. In ovariectomized Fut2-LacZ mice, estradiol treatment stimulates X-gal staining in endocervix and uterus but does not affect expression in stomach and colon. Northern blot analysis in wild-type mice shows 15-fold elevations of Fut2 steady-state mRNA with estradiol treatment, whereas Fut1 varies little. Fut2 levels in the glandular stomach and distal colon remain constant, and uterine Fut2 levels vary eightfold during the estrous cycle. These data represent the first demonstration of a glycosyltransferase gene under tissue-specific hormonal regulation in a LacZ reporter mouse model. Endocervical expression of Fut2 in estrus and pregnancy may modify cervical mucus barrier properties from microbial infection analogous to the potential role of mucosal glycans in humans. Key words: endocervical glands / fucosyltransferase / glandular stomach / mucus
|
Introduction |
|---|
|
TopAbstractIntroductionResultsDiscussionMaterials and methodsReferences |
|---|
Posttranslational modification of cellular glycans with fucose is essential to embryonic growth and development, fertility, and immune function (Smith et al., 2002
). The enzymes responsible for synthesis of fucosylated glycans, called fucosyltransferases, are expressed in tissue-specific patterns. Alterations in the expression of fucosylated glycans and their cognate fucosyltransferases have been observed in multiple pathologic processes involving inflammation, cancer, and numerous ontogenic events involving signaling events by the Notch receptor family (Becker and Lowe, 2003). Mouse embryos lacking the protein O-fucosyltransferase 1 of the Notch pathway die at mid-gestation (Shi and Stanley, 2003).
Classes of fucosyltransferase are divided by the glycosidic linkage catalyzed (Breton et al., 1998). FUT2, the secretor gene, encodes an (1,2)fucosyltransferase (E.C. 2.4.1.69) found in mucosal epithelium of buccal, gastrointestinal, respiratory, breast, and genitourinary tracts of humans and other mammals. Polymorphism of FUT2 is well recognized and is associated with a number of inactivating mutations (Oriol et al., 2000). Approximately 20% of various populations are homozygous for enzyme-inactivating mutations, called nonsecretors, lack (1,2)fucose residues on secreted mucins. The function(s) of FUT2 remains controversial, but polymorphism of this gene has been proposed to be of medical importance because absence of a functional (1,2)fucosyltransferase in mucosal tissues is associated with differences in susceptibility to microbial infections, inflammation, and malignancy (D'Adamo and Kelly, 2001; Ishitoya et al., 2002; Lindesmith et al., 2003; Marionneau et al., 2002; Ronchetti et al.,2001).
In the reproductive tract, expression of specific uterine glycans vary during the ovulatory cycle (Carson, 2002; Kimber et al., 2001). Correlated with alterations in the hydrodynamic properties of cervical mucus, cervical mucins show changes in oligosaccharide structures during the ovulatory cycle (Argueso et al., 2002; Yurewicz et al., 1987). In women, nonsecretor status is associated with recurrent vulvovaginal candidiasis (Chaim et al., 1997), whereas absence of a functional FUT2 gene was associated with reduced risk of HIV-1 infection (Ali et al., 2000) suggesting that alterations in vaginal mucosal immunity are associated with expression of FUT2, either increased or decreased susceptibility depending on the pathogen.
Despite the large number of fucosylated glycans and proposed biological functions, little is know about the regulation of their expression. Because FUT2 is expressed in both gastrointestinal and reproductive tracts, we investigated the hormonal regulation and cell type of expression of Fut2 in a mutant lacZ reporter mouse expressing the bacterial reporter gene lacZ under the endogenous promoter for Fut2.
|
Results |
|---|
|
TopAbstractIntroductionResultsDiscussionMaterials and methodsReferences |
|---|
Fut2-Lacz reporter gene in mutant mice identifies uterine and endocervical glandular cell expression under estrogen regulation
The cell type and regulation of expression of Fut2 was investigated in mice with a targeted mutation of Fut2 that replaced 98% of the Fut2 open reading frame with a nuclear-localizing bacterial reporter gene lacZ (Domino et al., 2001a
). In mice homozygous for the Fut2-LacZ fusion gene, X-gal staining reveals specific nuclear staining with blue precipitate in glandular and lumenal uterine epithelial cells (Figure 1A). Lumenal cell expression varies in intensity within the uterus during estrus and is almost completely absent in diestrus (Figure 1C). In contrast, glandular epithelium staining is consistently strong between replicate experiments but also shows decreased expression from estrus to diestrus. Uterine tissues from wild-type mice are negative for X-gal staining in estrus and diestrus (Figure 1B and D).
|
The effects of estradiol and progesterone treatments on LacZ expression were examined in ovariectomized Fut2-LacZ mice. Because previous northern blot data demonstrated Fut2 expression in stomach and colon, X-gal staining was examined in these tissues as well as uterus. X-gal staining of stomach from Fut2-LacZ mice is positive irrespective of hormone replacement (Figure 2A, C, and E). In uterus, X-gal staining is negative with corn oil vehicle (Figure 2B) and estrogen-primed progesterone treatment (Figure 2D). However, with estradiol treatment, X-gal staining is grossly observed from cervix to uterine horns (Figure 2F). Tissues from ovariectomized wild-type mice treated with estradiol are negative for X-gal staining (Figure 2G and H). Colon shows a pattern of X-gal staining unresponsive to hormone treatments, identical to stomach (data not shown). Vagina, ovary, and oviduct do not show specific X-gal staining (data not shown).
|
To investigate the cell type of expression, microscopic examination of uterine and gastrointestinal tissues were performed following whole-organ X-gal staining. In uterus, specific X-gal staining of both lumenal and glandular epithelial cells is seen with estradiol treatment (Figure 3A), whereas estrogen-treated wild-type mice show no staining (Figure 3B). Fut2-LacZ mice treated with estrogen-primed progesterone (Figure 3C) or corn oil (Figure 3D) remain negative for X-gal expression.
|
In gastrointestinal tissues, microscopic examination of glandular stomach of Fut2-LacZ mice reveals specific LacZ expression in mucous-secreting foveolar pit and chief cells, whereas parietal cells are negative (Figure 4A). In colon, goblet cells stain densely with X-gal (Figure 4C). Corresponding sections from wild-type mouse stomach and colon are negative for X-gal staining (Figure 4B and D).
|
Fut2-LacZ expression during pregnancy is restricted to endocervical glands
X-gal staining of uteri from mid-gestation (day 9.5) pregnant Fut2-LacZ mice reveals Fut2-LacZ expression restricted to the endocervix (Figure 5A). Microscopic sections of the uterus at a level between cervix and the most proximal embryo implantation site display minimal expression in glandular epithelium and no expression in lumenal epithelium (Figure 5C). No LacZ expression is seen in implantation sites or placental tissues (not shown), or in tissues from wild-type pregnant mice (Figure 5B and D). Identical results are seen in late-gestation mice (day 16.5; not shown).
|
Wild-type mice confirm hormonal regulation of Fut2, but not Fut1, steady-state mRNA levels
To confirm the hormonal regulation of the Fut2 locus in wild-type mice, northern blot analyses were performed using probes specific for Fut2 and a second
(1,2)fucosyltransferase expressed in uterus (Fut1) (Domino et al., 2001b). For mRNA loading controls, ribosomal protein L32 and cyclophillin-A were tested for suitability because more common standardization genes, such as ß-actin and glyceraldehyde phosphate dehydrogenase, are much more abundant than Fut2 mRNA. Both L32 and cyclophillin-A mRNA display constitutive expression in uterus, stomach, and colon (data not shown). For further analyses, L32 mRNA was chosen to normalize variations in mRNA loading.
The effects of estradiol and estrogen-primed progesterone treatments on Fut2 and Fut1 steady-state mRNA levels were compared in ovariectomized mice. Analogous to X-gal staining in Fut2-LacZ mice, estradiol treatment of ovariectomized wild-type mice increases Fut2 expression 15-fold in uterus with no significant change by estrogen-primed progesterone treatment or estrogen plus progesterone (Figure 6A). Levels of Fut1 were tested because Fut1 was previously reported to be stimulated by estrogen in mouse uterus (Sidhu and Kimber, 1999) (those studies were published prior to the cloning of Fut2 and likely used a probe nonselective between Fut1 and Fut2). Using DNA probes selective for Fut1 versus Fut2, Fut1 mRNA levels do not significantly vary with hormone replacement (Figure 6B).
|
In naturally cycling wild-type mice, Fut2 uterine mRNA steady-state levels are highest in proestrus and estrus; elevated six- to eightfold compared to diestrus (Figure 7A). Metestrus levels are intermediate between estrus and diestrus. Relative to uterus, Fut2 mRNA levels are more highly expressed in stomach and colon, but do not vary significantly during the estrous cycle (Figure 7B and C).
|
|
Discussion |
|---|
|
TopAbstractIntroductionResultsDiscussionMaterials and methodsReferences |
|---|
Estrogens markedly enhance the rate of N-linked glycoprotein synthesis in the uterus by stimulating the glycosylation apparatus, including the mannosylphorphoryldolichol synthase pathway (Carson et al., 1990
). Among the terminal glycosyltransferases, we demonstrate differential regulation by estradiol of Fut2, but not Fut1, between hormonally responsive and nonresponsive tissues. X-gal staining in Fut2-LacZ mice recapitulates the hormonal control of the Fut2 locus in wild-type mice in a tissue-specific, cell type–restricted manner. These results represent the first direct demonstration of a glycosyltransferase gene under tissue-specific hormonal regulation in a LacZ reporter mouse model. The genomic elements required for this hormonal regulation are not disrupted by the presence of targeting vector sequences and do not require the Fut2 open reading frame or 3' region.
Localization of X-gal staining to glandular mucosa of the endocervix throughout pregnancy is an unexpected finding. In studies focusing on a potential role of fucosyltransferase genes in implantation, decreased fucosyltransferase expression was noted in early pregnancy (Sidhu and Kimber, 1999; White and Kimber, 1994). In this study, minimal levels of X-gal staining are seen in the gravid uterus. Prominent X-gal expression, however, is present in the endocervix. Because endocervical glands represent only a small portion of the total uterus on homogenization, previous northern blot analyses showing an overall decrease in expression during pregnancy are consistent with the data presented here.
Although Fut2-null mice were noted to display normal fertility eliminating an essential role for this gene in implantation, the endocervix was not studied (Domino et al., 2001a). Endocervical expression that varies during the estrous cycle and prominent expression during pregnancy suggests a potential protective role against ascending infection analogous to the hypothesized role of glycosyltransferases genes in the gastrointestinal tract (Henry, 2001). In humans, expression of fucosylated blood group antigens in cervical mucus and on the cell surface of vaginal cells vary cyclically in both secretor and nonsecretor women (Schaeffer et al., 1994). Because host–pathogen interactions frequently involve cell surface glycans as adhesion molecules, polymorphism of the secretor gene have been proposed to be associated with susceptibility to microbial infections (Varki, 1993). A role for FUT2 in modifying cervical mucus barrier properties is supported by epidemiological studies of woman showing variation with the nonsecretor polymorphism in the prevalence of recurrent vulvovaginal candidiasis with Candida albicans, and urinary tract infection by some strains of Escherichia coli (Chaim et al., 1997; Stapleton et al., 1995).
A possible mechanism for affect of FUT2 on microbe adhesion is alteration of cervical mucin glycosylation. Multiple mucin forms are expressed in endocervix and MUC5B expression varies with the ovulatory cycle (Gipson et al., 2001). Microbe binding could be altered by shifting the balance of mucin glycosylation between fucosylation and sulfation (Scharfman et al., 1996) similar to cystic fibrosis mice, which were found to have elevated Fut2 expression in intestine (Thomsson et al., 2002). Expression of the Fut2 cannot always be considered protective for mucosal immunity, however, because the risk of HIV-1 infection was increased in secretor women relative to nonsecretors (Ali et al., 2000). Other data suggest a positive effect on host–microbe interaction from the loss of FUT2, such as a lower incidence of Helicobacter pylori exposure in secretor-null individuals (Ikehara et al., 2001). An effect of hormonally regulated genes on sexually transmitted infections, whether protective or deleterious, appears to depend on the specific infecting organism (Brabin, 2002).
This study did not address whether regulation of Fut2 expression by estrogen is direct or indirect. Estrogen receptor- (ER-) has been reported to be present in mouse uterus throughout gestation, but with decreasing levels as gestation progressed (Spong et al., 2000). Both epithelial and stromal ER- were found to be necessary for the production of uterine secretory proteins (Buchanan et al., 1999). ER-ß subtype ligands also exerted an effect on some markers of estrogen action (Frasor et al., 2003). To consider potential transcriptional regulation, the 5' genomic regions of mouse and human Fut2 were searched for estrogen response consensus sequences. Although annotation of the human and mouse Fut2 genes are currently provisional, mouse Fut2 mRNA (NCBI RefSeq NM_018876) and human FUT2 mRNA (NCBI RefSeq NM_000511) were aligned to the respective genome sequence from the Mouse and Human Genome Consortiums using the UCSC Genome Bioinformatics Human Genome Browser Gateway (Karolchik et al., 2003). The corresponding genomic regions (6000 bp) 5' to exon 1 from mouse (chr7:34307353–34313352 minus strand, February 2003 freeze) and human (chr19:53853281 to 53859280 plus strand, April 2003 freeze) were scanned with the MacInspector program V2.2 using TRANFAC 4.0 matrixes (Wingender et al., 2000). No consensus estrogen response elements were found, although multiple weak partial matches to the half palindrome site GGTCA are present.
ER-mediated transcriptional regulation may, however, proceed through nonclassical ER-/Sp1 binding, where estrogen binds its receptor followed by binding to Sp1 transcription factors, which then directs the complex to a binding motif in the 5' region (Khan et al., 2003). Multiple potential Sp1 binding motifs were present in the Fut2 5' region along with dozens of potential transcription factor sites. Alternatively to transcriptional control, the 3' untranslated region of human Fut2 mRNA may form a large stem-and-loop structure (1.2 kb) potentially regulating the stability and level of the Fut2 transcript (Koda et al., 1997). Study of cells from Fut2-LacZ tissues would benefit from the relative ease of assay for LacZ and may help elucidate molecular mechanism of Fut2 hormonal regulation. The Fut2-LacZ mouse may also serve as a model of the human nonsecretor for testing the importance of cell surface (1,2)fucosylated glycans in host–microbe interactions.
|
Materials and methods |
|---|
|
TopAbstractIntroductionResultsDiscussionMaterials and methodsReferences |
|---|
Experimental animals and hormone treatments
Animal protocols were approved by the University of Michigan Committee on Use and Care of Animals. Groups of 12 mice, wild-type strain 129X1/SvJ (Jackson Laboratory, Bar Harbor, ME; stock no. 000691) or Fut2-LacZ mutant mice (Domino et al., 2001a
) (MGI accession ID 2183220, allele symbol Fut2tm1Sdo), age 8–9 weeks, were followed by examination of vaginal cytology to determine the stage of estrous cycle (Nelson et al., 1982). For hormone treatments, groups of eight mice were ovariectomized as described (Nagy et al., 2002). Two weeks later, all mice were injected IP daily for 3 days with a priming dose of 0.1 µg ß-estradiol (Sigma, St. Louis, MO; catalog no. E-8515). After a 2-day wait, mice were injected daily for 4 days with either 0.1 µg ß-estradiol, 500 µg progesterone (Sigma, catalog no. P-0130), estrogen and progesterone, or vehicle-only corn oil (White and Kimber, 1994). For experiments requiring pregnant mice, females were housed overnight with male studs and vaginal plugs checked to determine day 0.5 of pregnancy. Pregnancy was confirmed by the presence of multiple gestational sacs when mice were euthanized. The targeting vector and generation of Fut2-LacZ mutant mice was previously described (Domino et al., 2001a). In this study, the Fut2-LacZ homozygous mutant mice were on a hybrid 129X1/SvJ and C57BL/6 J background generation F3-F5.
X-gal staining
Control experiments for X-gal staining using wild-type strain 129X1/SvJ and strain C57BL/6 J (stock no. 000664) showed no background staining in the tissues tested. The experimental mutant mice, Fut2-LacZ, were on a hybrid 129X1/SvJ and C57BL/6 J background. To prepare tissues for X-gal staining, 8–9-week-old Fut2-LacZ and wild-type mice were terminally perfused with ice-cold phosphate buffered saline followed by freshly thawed 4% paraformaldehyde (Turkay et al., 1999). Tissues were excised, rinsed in phosphate buffered saline, then partially fixed in ice-cold 4% paraformaldyde for 20 min on ice with occasional shaking. Tissues were washed with 0.1 M sodium phosphate, pH 7.3, three times and stained with X-gal overnight at 37°C as described (Saunders, 2002). To preserve the blue X-gal precipitant, tissues were postfixed in 10% formalin and 0.2% glutaraldehyde overnight, then processed for paraffin sectioning and nuclear fast red staining avoiding all organic solvents (Histoserv, Germantown, MD). Whole-organ pictures were photographed with a 35 mm macrolens.
Northern blot analysis
Total RNA was isolated by the guanidine isothiocyanate/phenol method (TRIzol; GibcoBRL, Grand Island, NY) followed by isolation of polyadenylated RNA by Oligotex midi mRNA columns (Qiagen, Valencia, CA). Colon samples were taken from the mid-portion of the large intestine of each animal. Independently isolated samples from individual mice containing 5 µg polyadenylated RNA were run on formaldehyde agarose gels, transferred to nylon, and hybridized with 32P-dCTP random primed DNA probes specific for Fut1 and Fut2 exactly as previously described (Domino et al., 2001b). Blots were stripped and hybridized with probes for either ribosomal protein L32 (113-bp probe purified from a Hind III digestion of mouse L32 template; BD Biosciences Pharmingen, San Diego, CA; no. 45181P) or cyclophillin-A (Ambion, Austin, TX; mouse DECAprobe template no.7375). A PhosphorImager Model SP was used to visualize and quantify northern blot radioactivity (Amersham Biosciences, Piscataway, NJ). Northern blot data were normalized to the level of L32 in each lane. One-way analysis of variance with Dunnett's multiple comparison test was performed using GraphPad Prism version 3.00 for Windows (GraphPad Software, San Diego, CA).
|
Acknowledgements |
|---|
We thank personnel of Histoserv for histology processing. We thank the University of Michigan Transgenic Animal Model core for assistance with ovariectomies and management of the Fut2-LacZ mice. This work was supported in part by NIH grants HD01195, CA93856, and a University of Michigan Rackham Grant (S.E.D.). E.A.H is a recipient of a University of Michigan Biomedical Research Council postdoctoral fellowship award.
|
Footnotes |
|---|
1 To whom correspondence should be addressed; e-mail: sedomino{at}med.umich.edu
|
Abbreviations |
|---|
ER, estrogen receptor
|
References |
|---|
|
TopAbstractIntroductionResultsDiscussionMaterials and methodsReferences |
|---|
Ali, S., Niang, M.A., N'Doye, I., Critchlow, C.W., Hawes, S.E., Hill, A.V., and Kiviat, N.B. (2000) Secretor polymorphism and human immunodeficiency virus infection in Senegalese women. J. Infect. Dis., 181, 737–739.[CrossRef][Web of Science][Medline]
Argueso, P., Spurr-Michaud, S., Tisdale, A., and Gipson, I.K. (2002) Variation in the amount of T antigen and N-acetyllactosamine oligosaccharides in human cervical mucus secretions with the menstrual cycle. J. Clin. Endocrinol. Metab., 87, 5641–5648.
Becker, D.J. and Lowe, J.B. (2003) Fucose: biosynthesis and biological function in mammals. Glycobiology, 13, 41R–53R.
Brabin, L. (2002) Interactions of the female hormonal environment, susceptibility to viral infections, and disease progression. AIDS Patient Care Stds, 16, 211–221.[CrossRef][Web of Science][Medline]
Breton, C., Oriol, R., and Imberty, A. (1998) Conserved structural features in eukaryotic and prokaryotic fucosyltransferases. Glycobiology, 8, 87–94.
Buchanan, D.L., Setiawan, T., Lubahn, D.B., Taylor, J.A., Kurita, T., Cunha, G.R., and Cooke, P.S. (1999) Tissue compartment-specific estrogen receptor-alpha participation in the mouse uterine epithelial secretory response. Endocrinology, 140, 484–491.
Carson, D.D. (2002) The glycobiology of implantation. Front. Biosci., 7, 1535–1544.
Carson, D.D., Farrar, J.D., Laidlaw, J., and Wright, D.A. (1990) Selective activation of the N-glycosylation apparatus in uteri by estrogen. J. Biol. Chem., 265, 2947–2955.
Chaim, W., Foxman, B., and Sobel, J.D. (1997) Association of recurrent vaginal candidiasis and secretory ABO and Lewis phenotype. J. Infect. Dis., 176, 828–830.[Web of Science][Medline]
D'Adamo, P.J. and Kelly, G.S. (2001) Metabolic and immunologic consequences of ABH secretor and Lewis subtype status. Alt. Med. Rev., 6, 390–405.
Domino, S.E., Zhang, L., Gillespie, P.J., Saunders, T.L., and Lowe, J.B. (2001a) 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. Mol. Cell. Biol., 21, 8336–8345.
Domino, S.E., Zhang, L., and Lowe, J.B. (2001b) Molecular cloning, genomic mapping, and expression of two secretor blood group alpha (1,2)fucosyltransferase genes differentially regulated in mouse uterine epithelium and gastrointestinal tract. J. Biol. Chem., 276, 23748–23756.
Frasor, J., Barnett, D.H., Danes, J.M., Hess, R., Parlow, A.F., and Katzenellenbogen, B.S. (2003) Response-specific and ligand dose-dependent modulation of estrogen receptor (ER) alpha activity by ERbeta in the uterus. Endocrinology, 144, 3159–3166.
Gipson, I.K., Moccia, R., Spurr-Michaud, S., Argueso, P., Gargiulo, A.R., Hill, J.A. III, Offner, G.D., and Keutmann, H.T. (2001) The amount of MUC5B mucin in cervical mucus peaks at midcycle. J. Clin. Endocrinol. Metab., 86, 594–600.
Henry, S.M. (2001) Molecular diversity in the biosynthesis of GI tract glycoconjugates. A blood-group-related chart of microorganism receptors. Transfus. Clin. Biol., 8, 226–230.[CrossRef][Web of Science][Medline]
Ikehara, Y., Nishihara, S., Yasutomi, H., Kitamura, T., Matsuo, K., Shimizu, N., Inada, K., Kodera, Y., Yamamura, Y., Narimatsu, H., and others. (2001) Polymorphisms of two fucosyltransferase genes (Lewis and Secretor genes) involving type I Lewis antigens are associated with the presence of anti-Helicobacter pylori IgG antibody. Cancer Epidemiol. Biomarkers Prev., 10, 971–977.
Ishitoya, S., Yamamoto, S., Mitsumori, K., Ogawa, O., and Terai, A. (2002) Non-secretor status is associated with female acute uncomplicated pyelonephritis. BJU Int., 89, 851–854.[CrossRef][Web of Science][Medline]
Karolchik, D., Baertsch, R., Diekhans, M., Furey, T.S., Hinrichs, A., Lu, Y.T., Roskin, K.M., Schwartz, M., Sugnet, C.W., Thomas, D.J., and others. (2003) The UCSC genome browser database. Nucleic Acids Res., 31, 51–54.
Khan, S., Abdelrahim, M., Samudio, I., and Safe, S. (2003) Estrogen receptor/Sp1 complexes are required for induction of cad gene expression by 17beta-estradiol in breast cancer cells. Endocrinology, 144, 2325–2335.
Kimber, S.J., Stones, R.E., and Sidhu, S.S. (2001) Glycosylation changes during differentiation of the murine uterine epithelium. Biochem. Soc. Trans., 29, 156–162.[CrossRef][Web of Science][Medline]
Koda, Y., Soejima, M., Wang, B., and Kimura, H. (1997) Structure and expression of the gene encoding secretor-type galactoside 2-alpha-L-fucosyltransferase (FUT2). Eur. J. Biochem., 246, 750–755.[Web of Science][Medline]
Lindesmith, L., Moe, C., Marionneau, S., Ruvoen, N., Jiang, X., Lindblad, L., Stewart, P., LePendu, J., and Baric, R. (2003) Human susceptibility and resistance to Norwalk virus infection. Nat. Med., 9, 548–553.[CrossRef][Web of Science][Medline]
Marionneau, S., Ruvoen, N., Le Moullac-Vaidye, B., Clement, M., Cailleau-Thomas, A., Ruiz-Palacois, G., Huang, P., Jiang, X., and Le Pendu, J. (2002) Norwalk virus binds to histo-blood group antigens present on gastroduodenal epithelial cells of secretor individuals. Gastroenterology, 122, 1967–1977.[CrossRef][Web of Science][Medline]
Nagy, A., Behringer, R., Gertsenstein, M., and Vintersten, K. (2002) Manipulating the mouse embryo: a laboratory manual, 3rd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
Nelson, J.F., Felicio, L.S., Randall, P.K., Sims, C., and Finch, C.E. (1982) A longitudinal study of estrous cyclicity in aging C57BL/6 J mice: I. Cycle frequency, length and vaginal cytology. Biol. Reprod., 27, 327–339.[Abstract]
Oriol, R., Candelier, J.J., and Mollicone, R. (2000) Molecular genetics of H. Vox. Sang., 78, 105–108.[Medline]
Ronchetti, F., Villa, M.P., Ronchetti, R., Bonci, E., Latini, L., Pascone, R., Bottini, N., and Gloria-Bottini, F. (2001) ABO/Secretor genetic complex and susceptibility to asthma in childhood. Eur. Resp. J., 17, 1236–1238.
Saunders, T.L. (2002) Reporter molecules in genetically engineered mice. In Hofker, M.H. and van Deursen, J. (Eds.), Methods in molecular biology: transgenic mouse methods and protocols. Humana Press, Totowa, NJ, pp. 125–143.
Schaeffer, A.J., Navas, E.L., Venegas, M.F., Anderson, B.E., Kanerva, C., Chmiel, J.S., and Duncan, J.L. (1994) Variation of blood group antigen expression on vaginal cells and mucus in secretor and nonsecretor women. J. Urol., 152, 859–864.[Web of Science][Medline]
Scharfman, A., Van Brussel, E., Houdret, N., Lamblin, G., and Roussel, P. (1996) Interactions between glycoconjugates from human respiratory airways and Pseudomonas aeruginosa. Am. J. Resp. Crit. Care Med., 154, S163–169.[Web of Science][Medline]
Shi, S. and Stanley, P. (2003) Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways. Proc. Natl Acad. Sci. USA, 100, 5234–5239.
Sidhu, S.S. and Kimber, S.J. (1999) Hormonal control of H-type alpha (1-2)fucosyltransferase messenger ribonucleic acid in the mouse uterus. Biol. Reprod., 60, 147–157.
Smith, P.L., Myers, J.T., Rogers, C.E., Zhou, L., Petryniak, B., Becker, D.J., Homeister, J.W., and Lowe, J.B. (2002) Conditional control of selectin ligand expression and global fucosylation events in mice with a targeted mutation at the FX locus. J. Cell Biol., 158, 801–815.
Spong, C.Y., McCune, S.K., Sternberg, E.M., and Gustafsson, J.A. (2000) Maternal estrogen receptor-beta expression during mouse gestation. Am. J. Reprod. Immunol., 44, 249–252.[Medline]
Stapleton, A., Hooton, T.M., Fennell, C., Roberts, P.L., and Stamm, W.E. (1995) Effect of secretor status on vaginal and rectal colonization with fimbriated Escherichia coli in women with and without recurrent urinary tract infection. J. Infect. Dis., 171, 717–720.[Web of Science][Medline]
Thomsson, K.A., Hinojosa-Kurtzberg, M., Axelsson, K.A., Domino, S.E., Lowe, J.B., Gendler, S.J., and Hansson, G.C. (2002) Intestinal mucins from cystic fibrosis mice show increased fucosylation due to an induced Fucalpha1-2 glycosyltransferase. Biochem. J., 367, 609–616.[CrossRef][Web of Science][Medline]
Turkay, A., Saunders, T., and Kurachi, K. (1999) Intrauterine gene transfer: gestational stage-specific gene delivery in mice. Gene Ther., 6, 1685–1694.[CrossRef][Web of Science][Medline]
Varki, A. (1993) Biological roles of oligosaccharides: all of the theories are correct. Glycobiology, 3, 97–130.
White, S. and Kimber, S.J. (1994) Changes in alpha (1-2)-fucosyltransferase activity in the murine endometrial epithelium during the estrous cycle, early pregnancy, and after ovariectomy and hormone replacement. Biol. Reprod., 50, 73–81.[Abstract]
Wingender, E., Chen, X., Hehl, R., Karas, H., Liebich, I., Matys, V., Meinhardt, T., Pruss, M., Reuter, I. and Schacherer, F. (2000) TRANSFAC: an integrated system for gene expression regulation. Nucleic Acids Res., 28, 316–319.
Yurewicz, E.C., Matsuura, F., and Moghissi, K.S. (1987) Structural studies of sialylated oligosaccharides of human midcycle cervical mucin. J. Biol. Chem., 262, 4733–4739.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. A. Hurd, J. M. Holmen, G. C. Hansson, and S. E. Domino Gastrointestinal mucins of Fut2-null mice lack terminal fucosylation without affecting colonization by Candida albicans Glycobiology, October 1, 2005; 15(10): 1002 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Hurd and S. E. Domino Increased Susceptibility of Secretor Factor Gene Fut2-Null Mice to Experimental Vaginal Candidiasis Infect. Immun., July 1, 2004; 72(7): 4279 - 4281. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||