title: Loss of APC function in mesenchymal cells surrounding the Müllerian duct leads to myometrial defects in adult mice.
abstract: The WNT signal transduction pathway plays a rate limiting role in early development of many different organs. To study the functional consequences of constitutive activation of the canonical WNT pathway in the developing uterus, we generated a novel mouse model where loss of the tumor suppressor gene Apc was induced. A mouse model was generated and evaluated where Amhr2(Cre/+) driven loss of Apc exon 15 was induced. The Apc recombination was detected mainly in the myometrial layer of the adult uterus. A significant loss of muscle fibers in myometrium was apparent, though with very few muscle cells earmarked by nuclear β-catenin. The finding was confirmed in the Pgr(Cre/+);Apc(15lox/15lox) mouse model. Loss of APC function in mesenchymal cells surrounding the fetal Müllerian ducts results in severe defects in the myometrial layers of the uterus in adult mice, suggesting that the WNT signaling pathway plays important roles in maintaining myometrial integrity.
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, The Netherlands. youtheewang@hotmail.com
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Wang
authors.forename: Yundan
authors.initials: Y
authors.lastname: Jia
authors.forename: Patrick
authors.initials: P
authors.lastname: Franken
authors.forename: Ron
authors.initials: R
authors.lastname: Smits
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Ewing
authors.forename: John P
authors.initials: JP
authors.lastname: Lydon
authors.forename: Francesco J
authors.initials: FJ
authors.lastname: DeMayo
authors.forename: Curt W
authors.initials: CW
authors.lastname: Burger
authors.forename: J
authors.initials: J
authors.lastname: Anton Grootegoed
authors.forename: Riccardo
authors.initials: R
authors.lastname: Fodde
authors.forename: Leen J
authors.initials: LJ
authors.lastname: Blok
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004717:Endometrium / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D005260:Female; D055786:Gene Knockout Techniques; D017930:Genes, Reporter; D008648:Mesoderm / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009095:Mullerian Ducts / Q000473:pathology*; D009215:Myometrium / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D018000:Receptors, Peptide / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; C084621:anti-Mullerian hormone receptor; D001616:beta-Galactosidase