title: An update to the list of mouse mutants with neural tube closure defects and advances toward a complete genetic perspective of neural tube closure.
abstract: The number of mouse mutants and strains with neural tube defects (NTDs) now exceeds 240, including 205 representing specific genes, 30 for unidentified genes, and 9 multifactorial strains. These mutants identify genes needed for embryonic neural tube closure. Reports of 50 new NTD mutants since our 2007 review (Harris and Juriloff, 2007) were considered in relation to the previously reviewed mutants to obtain new insights into mechanisms of NTD etiology. In addition to null mutations, some are hypomorphs or conditional mutants. Some mutations do not cause NTDs on their own, but do so in digenic, trigenic, and oligogenic combinations, an etiology that likely parallels the nature of genetic etiology of human NTDs. Mutants that have only exencephaly are fourfold more frequent than those that have spina bifida aperta with or without exencephaly. Many diverse cellular functions and biochemical pathways are involved; the NTD mutants draw new attention to chromatin modification (epigenetics), the protease-activated receptor cascade, and the ciliopathies. Few mutants directly involve folate metabolism. Prevention of NTDs by maternal folate supplementation has been tested in 13 mutants and reduces NTD frequency in six diverse mutants. Inositol reduces spina bifida aperta frequency in the curly tail mutant, and three new mutants involve inositol metabolism. The many NTD mutants are the foundation for a future complete genetic understanding of the processes of neural fold elevation and fusion along mechanistically distinct cranial-caudal segments of the neural tube, and they point to several candidate processes for study in human NTD etiology.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada. mjharris@interchange.ubc.ca
authors.forename: Muriel J
authors.initials: MJ
authors.lastname: Harris
authors.forename: Diana M
authors.initials: DM
authors.lastname: Juriloff
mesh_terms: D000818:Animals; D002925:Ciliary Motility Disorders / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D004195:Disease Models, Animal; D057890:Epigenomics; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism; D009436:Neural Tube Defects / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D044462:Receptors, Proteinase-Activated / Q000235:genetics / Q000378:metabolism
chemical_list: D044462:Receptors, Proteinase-Activated; D007294:Inositol; D005492:Folic Acid