| First Author | Karner CM | Year | 2010 |
| Journal | PLoS One | Volume | 5 |
| Issue | 4 | Pages | e10418 |
| PubMed ID | 20454682 | Mgi Jnum | J:160547 |
| Mgi Id | MGI:4454602 | Doi | 10.1371/journal.pone.0010418 |
| Citation | Karner CM, et al. (2010) Lrp4 regulates initiation of ureteric budding and is crucial for kidney formation--a mouse model for Cenani-Lenz syndrome. PLoS One 5(4):e10418 |
| abstractText | 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. |
