{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:17:20Z","timestamp":1790551040935,"version":"4.1.0"},"reference-count":29,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,4,15]]},"abstract":"<jats:p>\n                    We recently reported that a germ-line insertion in the rat homologue of the human tuberous sclerosis gene (\n                    <jats:italic>TSC2<\/jats:italic>\n                    ) gives rise to dominantly inherited cancer in the Eker rat model. In this study, we constructed transgenic Eker rats with introduction of a wild-type\n                    <jats:italic>Tsc2<\/jats:italic>\n                    gene to ascertain whether suppression of the Eker phenotype is possible. Rescue from embryonic lethality of mutant homozygotes (Eker\/Eker) and suppression of\n                    <jats:italic>N<\/jats:italic>\n                    -ethyl-\n                    <jats:italic>N<\/jats:italic>\n                    -nitrosourea-induced renal carcinogenesis in heterozygotes (Eker\/+) were both observed, defining the germ-line\n                    <jats:italic>Tsc2<\/jats:italic>\n                    mutation in the Eker rat as embryonal lethal and tumor predisposing mutation. To the best of our knowledge, this is the first report of rescue from a naturally occurring dominantly inherited cancer. This transgenic rescue system will be useful to analyze\n                    <jats:italic>Tsc2<\/jats:italic>\n                    gene function, its relation to tumorigenesis\n                    <jats:italic>in vivo<\/jats:italic>\n                    , and genetic\u2013environmental interactions in carcinogenesis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.8.3990","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:31:39Z","timestamp":1027679499000},"page":"3990-3993","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":54,"title":["Transgenic rescue from embryonic lethality and renal carcinogenesis in the Eker rat model by introduction of a wild-type\n                    <i>Tsc2<\/i>\n                    \u2009gene"],"prefix":"10.1073","volume":"94","author":[{"given":"Toshiyuki","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Department of Experimental Pathology, Cancer Institute, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170, Japan; YS New Technology Institute Inc., Shimotsuga-gun, Tochigi 329-05, Japan; and Laboratory of Animal Center, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo 173, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Mitani","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology, Cancer Institute, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170, Japan; YS New Technology Institute Inc., Shimotsuga-gun, Tochigi 329-05, Japan; and Laboratory of Animal Center, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo 173, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ri-ichi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology, Cancer Institute, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170, Japan; YS New Technology Institute Inc., Shimotsuga-gun, 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