title: Lrp4 regulates initiation of ureteric budding and is crucial for kidney formation--a mouse model for Cenani-Lenz syndrome.
abstract: BACKGROUND
  Development of the kidney is initiated when the ureteric bud (UB) branches from the Wolffian duct and invades the overlying metanephric mesenchyme (MM) triggering the mesenchymal/epithelial interactions that are the basis of organ formation. Multiple signaling pathways must be integrated to ensure proper timing and location of the ureteric bud formation.
  
  
  RESULTS
  We have used gene targeting to create an Lrp4 null mouse line. The mutation results in early embryonic lethality with a subpenetrant phenotype of kidney agenesis. Ureteric budding is delayed with a failure to stimulate the metanephric mesenchyme in a timely manner, resulting in failure of cellular differentiation and resulting absence of kidney formation in the mouse as well as comparable malformations in humans with Cenani-Lenz syndrome.
  
  
  CONCLUSIONS
  Lrp4 is a multi-functional receptor implicated in the regulation of several molecular pathways, including Wnt and Bmp signaling. Lrp4(-/-) mice show a delay in ureteric bud formation that results in unilateral or bilateral kidney agenesis. These data indicate that Lrp4 is a critical regulator of UB branching and lack of Lrp4 results in congenital kidney malformations in humans and mice.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Karner
authors.forename: Martin F
authors.initials: MF
authors.lastname: Dietrich
authors.forename: Eric B
authors.initials: EB
authors.lastname: Johnson
authors.forename: Natalie
authors.initials: N
authors.lastname: Kappesser
authors.forename: Christian
authors.initials: C
authors.lastname: Tennert
authors.forename: Ferda
authors.initials: F
authors.lastname: Percin
authors.forename: Bernd
authors.initials: B
authors.lastname: Wollnik
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Carroll
authors.forename: Joachim
authors.initials: J
authors.lastname: Herz
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004195:Disease Models, Animal; D006801:Humans; D007668:Kidney / Q000002:abnormalities / Q000196:embryology / Q000254:growth & development*; D007674:Kidney Diseases / Q000209:etiology; D026502:LDL-Receptor Related Proteins; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000502:physiology*; D015398:Signal Transduction; D013577:Syndrome; D014513:Ureter / Q000196:embryology / Q000254:growth & development*
chemical_list: D026502:LDL-Receptor Related Proteins; C116415:Lrp4 protein, mouse; D011973:Receptors, LDL
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