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Here, we provide the first genetic delineation of cholinergic nicotinic receptor alpha7 (<jats:italic>Chrna7<\/jats:italic>) expression and link the ablation of the <jats:italic>Chrna7<\/jats:italic> cell lineage to this condition in the mouse. Using homologous recombination, an IRES\u2010Cre bi\u2010cistronic cassette was introduced into the 3\u2032 noncoding region of <jats:italic>Chrna7<\/jats:italic> (<jats:italic>Chrna7:Cre<\/jats:italic>) for identifying cell lineages expressing this gene. This lineage first appears at embryonic day E9.0 in rhombomeres 3 and 5 of the neural tube and extends to cell subsets in most tissues by E14.5. Ablation of the <jats:italic>Chrna7:Cre<\/jats:italic> cell lineage in embryos from crosses with conditionally expressed attenuated diphtheria toxin results in precise developmental defects including omphalocele (89%) and open spina bifida (SB; 80%). We hypothesized that like humans, this defect would be modified by environmental compounds not only folic acid or choline but also nicotine. Prenatal chronic oral nicotine administration substantially worsened the defect to often include the rostral neural tube. In contrast, supplementation of the maternal diet with 2% choline decreased SB prevalence to 38% and dramatically reduced the defect severity. Folic acid supplementation only trended towards a reduced SB frequency. The omphalocele was unaffected by these interventions. These studies identify the <jats:italic>Chrna7<\/jats:italic> cell lineage as participating in posterior neuropore closure and present a novel model of lower SB that can be substantially modified by the prenatal environment. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.35372","type":"journal-article","created":{"date-parts":[[2012,4,3]],"date-time":"2012-04-03T13:34:59Z","timestamp":1333460099000},"page":"1135-1144","source":"Crossref","is-referenced-by-count":19,"title":["Prenatal ablation of nicotinic receptor alpha7 cell lineages produces lumbosacral spina bifida the severity of which is modified by choline and nicotine exposure"],"prefix":"10.1002","volume":"158A","author":[{"given":"Scott W.","family":"Rogers","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"Tvrdik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario R.","family":"Capecchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorise C.","family":"Gahring","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,3,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2009.12.049"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2008"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddrr.93"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.3.283"},{"key":"e_1_2_6_6_1","first-page":"253","article-title":"The OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects)","volume":"14","author":"Carey JC","year":"1978","journal-title":"Birth Defects Orig Artic Ser"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jada.2010.05.009"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-4-36"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.44.s3.2.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1208\/aapsj070486"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/1359105307074240"},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0140-6736(91)90133-A","article-title":"Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study. 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