{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:02:46Z","timestamp":1781107366166,"version":"3.54.1"},"reference-count":16,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,8,14]]},"abstract":"\n The forebrain overgrowth mutation (\n fog<\/jats:italic>\n ) was\n originally described as a spontaneous autosomal recessive mutation\n mapping to mouse chromosome 10 that produces forebrain defects, facial\n defects, and spina bifida. Although the\n fog<\/jats:italic>\n mutant has\n been characterized and available to investigators for several years,\n the underlying mutation causing the pathology has not been known.\n Because of its phenotypic resemblance to apoptotic protease\n activating factor-1 (Apaf-1) knockout mice, we have investigated the\n possibility that the\n fog<\/jats:italic>\n mutation is in the\n Apaf-1<\/jats:italic>\n gene. Allelic complementation, Western blot\n analysis, and caspase activation assays indicate that\n fog<\/jats:italic>\n mutant mice lack Apaf-1 activity. Northern blot and\n reverse transcription-PCR analysis show that\n Apaf-1<\/jats:italic>\n mRNA\n is aberrantly processed, resulting in greatly reduced expression levels\n of normal\n Apaf-1<\/jats:italic>\n mRNA. These findings are strongly\n suggestive of the\n fog<\/jats:italic>\n mutation being a hypomorphic\n Apaf-1<\/jats:italic>\n defect and implicate neural progenitor cell death\n in the pathogenesis of spina bifida\u2014a common human congenital\n malformation. Because a complete deficiency in\n Apaf-1<\/jats:italic>\n usually results in perinatal lethality and\n fog<\/jats:italic>\n \/\n fog<\/jats:italic>\n mice more readily survive into\n adulthood, these mutants serve as a valuable model with which\n apoptotic cell death can be studied\n in vivo<\/jats:italic>\n .\n <\/jats:p>","DOI":"10.1073\/pnas.171283198","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:37:36Z","timestamp":1027679856000},"page":"9683-9687","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":72,"title":["Apaf-1<\/i>\n deficiency and neural tube closure defects are found in\n fog<\/i>\n mice"],"prefix":"10.1073","volume":"98","author":[{"given":"Narimon","family":"Honarpour","sequence":"first","affiliation":[{"name":"Departments of Molecular Genetics and Biochemistry,\r and Howard Hughes Medical Institute, The University of\r Texas Southwestern Medical Center, Dallas, TX 75390-9046; and\r Department of Human Genetics, and Howard\r Hughes Medical Institute, University of Chicago, Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra L.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Biochemistry,\r and Howard Hughes Medical Institute, The University of\r Texas Southwestern Medical Center, Dallas, TX 75390-9046; and\r Department of Human Genetics, and Howard\r Hughes Medical Institute, University of Chicago, Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce T.","family":"Lahn","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Biochemistry,\r and Howard Hughes Medical Institute, The University of\r Texas Southwestern Medical Center, Dallas, TX 75390-9046; and\r Department of Human Genetics, and Howard\r Hughes Medical Institute, University of Chicago, Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Biochemistry,\r and Howard Hughes Medical Institute, The University of\r Texas Southwestern Medical Center, Dallas, TX 75390-9046; and\r Department of Human Genetics, and Howard\r Hughes Medical Institute, University of Chicago, Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Herz","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Biochemistry,\r and Howard Hughes Medical Institute, The University of\r Texas Southwestern Medical Center, Dallas, TX 75390-9046; and\r Department of Human Genetics, and Howard\r Hughes Medical Institute, University of Chicago, Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,8,14]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19991119)87:2<143::AID-AJMG6>3.0.CO;2-J"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.6.993"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199704)55:4<231::AID-TERA3>3.0.CO;2-3"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/384368a0"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81732-8"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81477-4"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81476-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81733-X"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1999.9585"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(97)01121-1"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(08)60610-X"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80501-2"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80085-9"},{"key":"e_1_3_3_14_2","first-page":"721","volume-title":"Molecular Cloning: A Laboratory Manual","author":"Sambrook J","year":"2001","unstructured":"J Sambrook, D W Russell Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Lab. Press, 3rd Ed., Plainview, New York), pp. 721\u2013745 (2001).","edition":"3"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00389540"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/35051606"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.171283198","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T02:58:36Z","timestamp":1649818716000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.171283198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,8,14]]},"references-count":16,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2001,8,14]]}},"alternative-id":["10.1073\/pnas.171283198"],"URL":"https:\/\/doi.org\/10.1073\/pnas.171283198","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,8,14]]},"assertion":[{"value":"2001-04-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-06-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-08-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}