| First Author | Carter M | Year | 2005 |
| Journal | Proc Natl Acad Sci U S A | Volume | 102 |
| Issue | 36 | Pages | 12843-8 |
| PubMed ID | 16126904 | Mgi Jnum | J:101423 |
| Mgi Id | MGI:3603992 | Doi | 10.1073/pnas.0501963102 |
| Citation | Carter M, et al. (2005) Crooked tail (Cd) model of human folate-responsive neural tube defects is mutated in Wnt coreceptor lipoprotein receptor-related protein 6. Proc Natl Acad Sci U S A 102(36):12843-8 |
| abstractText | A cranial neural tube defect in Crooked tail (Cd) mice is prevented with prenatal dietary folic acid Cd positional cloning reveals a missense mutation of a highly conserved amino acid in the low density lipoprotein receptor-related protein 6 (Lrp6), a coreceptor required for Wnt canonical signaling. Molecular modeling predicts that Lrp6(Cd) alters a hinge region of the second YWTD beta-propeller domain. Mutant LRP6 binds to Wnt and Dickkopf1 (Dkk1) but not Mesd1, and Dkk1 cannot antagonize Wnt in Cd/Cd cells, resulting in hyperactivity. NIH 3T3 cells transfected with a mutant Lrp6 plasmid resist Dkk1 antagonism much like Cd/+ cells, confirming the significance of the mutation. The Lrp6 mutation in Cd mice provides evidence for a functional connection between Wnt signaling and folate rescue of neural tube defects. |
