Crooked tail (Cd) model of human folate-responsive neural tube defects is mutated in Wnt coreceptor lipoprotein receptor-related protein 6 Academic Article uri icon


MeSH Major

  • Folic Acid
  • Intercellular Signaling Peptides and Proteins
  • Neural Tube Defects
  • Receptors, LDL
  • Tail


  • 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.

publication date

  • September 6, 2005



  • Academic Article



  • eng

PubMed Central ID

  • PMC1200260

Digital Object Identifier (DOI)

  • 10.1073/pnas.0501963102

PubMed ID

  • 16126904

Additional Document Info

start page

  • 12843

end page

  • 8


  • 102


  • 36