Loop-tail mouse model displays open and closed caudal neural tube defects.

Neural tube defects (NTDs) are the second most common cause of birth defects and are often studied in animal models. Loop-tail mice carry a mutation in the Vangl2 gene, member of the Wnt-PCP pathway. In Vangl2+/Lp embryos, the mutation induces a failure in the completion of the caudal neural tube closure but only a small percentage of embryos develop open spina bifida. Here, we showed that the majority of Vangl2+/Lp embryos develop caudal closed NTDs and present cellular aggregates that may facilitate the sealing of these defects. The cellular aggregates expressed neural crest cell markers and, using this as a readout, we described a systematic method to assess the severity of the neural tube dorsal fusion failure. We observed that this defect worsened in combination with other NTD mutants, Daam1 and Grhl3. Besides, we found that in Vangl2+/Lp embryos these NTDs were resistant to maternal folic acid and inositol supplementation. Loop-tail mice provide a useful model for research on the molecular interactions involved in the development of open and closed NTDs and for the design of prevention strategies for these diseases.