Mouse mutants with neural tube closure defects and their role in understanding human neural tube defects.

摘要: BACKGROUND: The number of mouse mutants and strains with neural tube closure defects (NTDs) now exceeds 190, including 155 involving known genes, 33 unidentified eight “multifactorial” strains. METHODS: emerging patterns NTDs are considered in relation to the unknown genetics common human NTDs, anencephaly, spina bifida aperta. RESULTS: Of 150 that survive past midgestation, 20% have risk either exencephaly aperta or both, parallel majority whereas 70% only exencephaly, 5% bifida, craniorachischisis. primary defect most is failure fold elevation. Most null mutations (>90%) produce syndromes multiple affected structures high penetrance homozygotes, several null-mutant heterozygotes partial gene function (hypomorphs) low-penetrance nonsyndromic like NTDs. normal functions mutated genes diverse, clusters pathways actin function, apoptosis, chromatin methylation structure. female excess observed anencephaly found all for which gender has been studied. Maternal agents, folate, methionine, inositol, alternative commercial diets, specific preventative effects CONCLUSIONS: If homologs NTD contribute it seems likely be multifactorial combinations hypomorphs heterozygotes, as exemplified by digenic oligogenic SELH/Bc strain. Birth Defects Research (Part A), 2007. © 2006 Wiley-Liss, Inc.