{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:30:00Z","timestamp":1787005800839,"version":"build-2736575974"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,3,2]]},"abstract":"<jats:p>\n                    Mutations in the human presenilin genes\n                    <jats:italic>PS1<\/jats:italic>\n                    and\n                    <jats:italic>PS2<\/jats:italic>\n                    cause early-onset Alzheimer\u2019s disease. Studies in\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    and in mice indicate that one function of presenilin genes is to facilitate Notch-pathway signaling. Notably, mutations in the\n                    <jats:italic>C. elegans<\/jats:italic>\n                    presenilin gene\n                    <jats:italic>sel-12<\/jats:italic>\n                    reduce signaling through an activated version of the Notch receptor LIN-12. To investigate the function of a second\n                    <jats:italic>C. elegans<\/jats:italic>\n                    presenilin gene\n                    <jats:italic>hop-1<\/jats:italic>\n                    and to examine possible genetic interactions between\n                    <jats:italic>hop-1<\/jats:italic>\n                    and\n                    <jats:italic>sel-12<\/jats:italic>\n                    , we used a reverse genetic strategy to isolate deletion alleles of both loci. Animals bearing both\n                    <jats:italic>hop-1<\/jats:italic>\n                    and\n                    <jats:italic>sel-12<\/jats:italic>\n                    deletions displayed new phenotypes not observed in animals bearing either single deletion. These new phenotypes\u2014germ-line proliferation defects, maternal-effect embryonic lethality, and somatic gonad defects\u2014resemble those resulting from a reduction in signaling through the\n                    <jats:italic>C. elegans<\/jats:italic>\n                    Notch receptors GLP-1 and LIN-12. Thus SEL-12 and HOP-1 appear to function redundantly in promoting Notch-pathway signaling. Phenotypic analyses of\n                    <jats:italic>hop-1<\/jats:italic>\n                    and\n                    <jats:italic>sel-12<\/jats:italic>\n                    single and double mutant animals suggest that\n                    <jats:italic>sel-12<\/jats:italic>\n                    provides more presenilin function than does\n                    <jats:italic>hop-1.<\/jats:italic>\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.5.2497","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:39:15Z","timestamp":1027679955000},"page":"2497-2502","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":66,"title":["Reverse genetic analysis of\n                    <i>Caenorhabditis elegans<\/i>\n                    presenilins reveals redundant but unequal roles for\n                    <i>sel-<\/i>\n                    <i>12<\/i>\n                    and\n                    <i>hop-<\/i>\n                    <i>1<\/i>\n                    in Notch-pathway signaling"],"prefix":"10.1073","volume":"96","author":[{"given":"Bethany","family":"Westlund","sequence":"first","affiliation":[{"name":"Axys Pharmaceuticals, NemaPharm Group, 100 Kimball Way, South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianne","family":"Parry","sequence":"additional","affiliation":[{"name":"Axys Pharmaceuticals, NemaPharm Group, 100 Kimball Way, South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Clover","sequence":"additional","affiliation":[{"name":"Axys Pharmaceuticals, NemaPharm Group, 100 Kimball Way, South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Basson","sequence":"additional","affiliation":[{"name":"Axys Pharmaceuticals, NemaPharm Group, 100 Kimball Way, South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl D.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Axys Pharmaceuticals, NemaPharm Group, 100 Kimball Way, South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1999,3,2]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/375754a0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7638622"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/376775a0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(96)01030-2"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.119.1.55"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/377351a0"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.22.12204"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.25.14940"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-4624.1997.00012.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/387288a0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80244-5"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/77.1.71"},{"key":"e_1_3_3_13_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0091-679X(08)61382-5","volume-title":"Caenorhabditis elegans: Modern Biological Analysis of an Organism","author":"Anderson P","year":"1995","unstructured":"P Anderson Caenorhabditis elegans: Modern Biological Analysis of an Organism, eds H F Epstein, D C Shakes (Academic, San Diego) 48, 31\u201358 (1995)."},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.4.1381"},{"key":"e_1_3_3_15_2","volume-title":"The Nematode Caenorhabditis elegans","author":"Wood W B","year":"1988","unstructured":"W B Wood The Nematode Caenorhabditis elegans (Cold Spring Harbor Lab. 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