Mouse models for neural tube closure defects

Area of Science:

• Developmental Biology
• Genetics
• Teratology

Background:

• Neural tube defects (NTDs), including anencephaly and spina bifida, affect 1 in 1000 newborns.
• Genetic complexity underlies NTDs, though periconceptional folic acid supplementation reduces risk.
• Over 60 mouse mutants with NTDs exist, exhibiting diverse genetic loci and inheritance patterns.

Purpose of the Study:

• To review and analyze existing mouse models of NTDs.
• To identify common functional pathways and genetic factors involved in neural fold elevation.
• To explore potential therapeutic targets for human NTDs.

Main Methods:

• Analysis of >60 mouse mutants and strains exhibiting NTDs.
• Review of genetic heterogeneity, penetrance, and inheritance patterns in NTD models.
• Examination of gene functions, including those involved in actin regulation and DNA methylation.

Main Results:

• Mouse NTD models frequently display exencephaly or spina bifida, indicating neural fold elevation failures.
• Nutrient supplements (folic acid, inositol, methionine) reduce NTD risk in specific models.
• Genes involved in actin regulation are frequently mutated in NTD models, highlighting their importance.
• Genes with basic mitotic functions also play a role in neural fold elevation.
• A potential link between DNA methylation and the female excess in cranial NTDs is suggested.

Conclusions:

• Actin regulation is a critical pathway for neural fold elevation and a promising area for human NTD gene discovery.
• Mouse models provide valuable insights into the complex genetics and mechanisms of NTDs.
• Further research into methylation and mitotic genes may elucidate additional NTD pathways.