An earlier version of the tables was presented at the Fourth International Conference on Neural Tube Defects, September 10–13, 2005, Indian Wells, California.
Mouse mutants with neural tube closure defects and their role in understanding human neural tube defects†
Article first published online: 19 DEC 2006
Copyright © 2006 Wiley-Liss, Inc.
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume 79, Issue 3, pages 187–210, March 2007
How to Cite
Harris, M. J. and Juriloff, D. M. (2007), Mouse mutants with neural tube closure defects and their role in understanding human neural tube defects. Birth Defects Research Part A: Clinical and Molecular Teratology, 79: 187–210. doi: 10.1002/bdra.20333
- Issue published online: 1 MAR 2007
- Article first published online: 19 DEC 2006
- Manuscript Revised: 20 OCT 2006
- Manuscript Accepted: 20 OCT 2006
- Manuscript Received: 15 SEP 2006
- Medical Research Council of Canada. Grant Number: MOP-6766
- Canadian Institutes of Health Research. Grant Number: IGI-60760
- neural tube defect;
- spina bifida;
- mouse model;
BACKGROUND: The number of mouse mutants and strains with neural tube closure defects (NTDs) now exceeds 190, including 155 involving known genes, 33 with unidentified genes, and eight “multifactorial” strains. METHODS: The emerging patterns of mouse NTDs are considered in relation to the unknown genetics of the common human NTDs, anencephaly, and spina bifida aperta. RESULTS: Of the 150 mouse mutants that survive past midgestation, 20% have risk of either exencephaly and spina bifida aperta or both, parallel to the majority of human NTDs, whereas 70% have only exencephaly, 5% have only spina bifida, and 5% have craniorachischisis. The primary defect in most mouse NTDs is failure of neural fold elevation. Most null mutations (>90%) produce syndromes of multiple affected structures with high penetrance in homozygotes, whereas the “multifactorial” strains and several null-mutant heterozygotes and mutants with partial gene function (hypomorphs) have low-penetrance nonsyndromic NTDs, like the majority of human NTDs. The normal functions of the mutated genes are diverse, with clusters in pathways of actin function, apoptosis, and chromatin methylation and structure. The female excess observed in human anencephaly is found in all mouse exencephaly mutants for which gender has been studied. Maternal agents, including folate, methionine, inositol, or alternative commercial diets, have specific preventative effects in eight mutants and strains. CONCLUSIONS: If the human homologs of the mouse NTD mutants contribute to risk of common human NTDs, it seems likely to be in multifactorial combinations of hypomorphs and low-penetrance heterozygotes, as exemplified by mouse digenic mutants and the oligogenic SELH/Bc strain. Birth Defects Research (Part A), 2007. © 2006 Wiley-Liss, Inc.