Lrp4 regulates initiation of ureteric budding and is crucial for kidney formation - a mouse model for cenani-lenz syndrome

Courtney M. Karner, Martin F. Dietrich, Eric B. Johnson, Natalie Kappesser, Christian Tennert, Ferda Percin, Bernd Wollnik, Thomas J. Carroll, Joachim Herz

Research output: Contribution to journalArticle

36 Citations (Scopus)

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. Methods and Principal Findings: 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. Conclusion: 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.

Original languageEnglish (US)
Article numbere10418
JournalPLoS One
Volume5
Issue number4
DOIs
StatePublished - 2010

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animal models
kidneys
Kidney
buds
Ducts
mice
Mesoderm
Genes
Wolffian Ducts
Wnt Signaling Pathway
Gene Targeting
gene targeting
branching
Syndromic 1 Microphthalmia
Phenotype
mutation
phenotype
Mutation
receptors
methodology

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lrp4 regulates initiation of ureteric budding and is crucial for kidney formation - a mouse model for cenani-lenz syndrome. / Karner, Courtney M.; Dietrich, Martin F.; Johnson, Eric B.; Kappesser, Natalie; Tennert, Christian; Percin, Ferda; Wollnik, Bernd; Carroll, Thomas J.; Herz, Joachim.

In: PLoS One, Vol. 5, No. 4, e10418, 2010.

Research output: Contribution to journalArticle

Karner, Courtney M. ; Dietrich, Martin F. ; Johnson, Eric B. ; Kappesser, Natalie ; Tennert, Christian ; Percin, Ferda ; Wollnik, Bernd ; Carroll, Thomas J. ; Herz, Joachim. / Lrp4 regulates initiation of ureteric budding and is crucial for kidney formation - a mouse model for cenani-lenz syndrome. In: PLoS One. 2010 ; Vol. 5, No. 4.
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