{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:10:08Z","timestamp":1788365408855,"version":"build-2803163510"},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,6,5]],"date-time":"2005-06-05T00:00:00Z","timestamp":1117929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2005,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The relevance of the <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min<\/jats:italic><\/jats:sup> mouse model in the study of human colorectal cancer remains uncertain due to the predominance of small intestinal adenomas and few, if any, colorectal adenomas. A new strain of <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min<\/jats:italic><\/jats:sup> mice (<jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010FCCC<\/jats:italic><\/jats:sup>) with significantly greater numbers of colorectal adenomas has been generated and characterized. Male C57BL\/6J\u2014<jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min<\/jats:italic><\/jats:sup> mice (the Jackson Laboratory, Bar Harbor, ME) were crossed with wild\u2010type <jats:italic>(Apc<\/jats:italic><jats:sup>+\/+<\/jats:sup>) C57BL\/6J females from an independent colony at this institution (offspring\u2009=\u2009<jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010FCCC<\/jats:italic><\/jats:sup>) and 233 animals were evaluated over 20 generations. In order to determine the contribution of genetics to the enhanced colorectal adenoma phenotype, breeding pairs (<jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min<\/jats:italic><\/jats:sup> male\u2009\u00d7\u2009wild type female C57BL\/6J) were purchased from the Jackson Laboratory and offspring (<jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010JAX<\/jats:italic><\/jats:sup>) were maintained in our facility under identical conditions (<jats:italic>n<\/jats:italic>\u2009=\u200998). Animals were fed Purina Rodent chow (#5013) diet containing 5% fat. The entire intestinal tract was examined histopathologically in both strains. Both the <jats:italic>Apc<\/jats:italic> and <jats:italic>Pla2g2a<\/jats:italic> (candidate for <jats:italic>Mom1<\/jats:italic>) genes were sequenced and found to be identical for both the <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010FCCC<\/jats:italic><\/jats:sup> and <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010JAX<\/jats:italic><\/jats:sup> mouse strains. The multiplicity of colorectal adenomas in the <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010FCCC<\/jats:italic><\/jats:sup> mice was much higher than reported in the literature and significantly greater than the multiplicity of colorectal adenomas in <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010JAX<\/jats:italic><\/jats:sup> mice maintained in our facility (<jats:italic>P<\/jats:italic>\u2009=\u20090.01). <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010FCCC<\/jats:italic><\/jats:sup> had a significantly greater incidence of rectal prolapse (<jats:italic>P<\/jats:italic>\u2009=\u20090.02) and small intestinal adenocarcinomes (<jats:italic>P<\/jats:italic>\u2009=\u20090.001), and multiplicity of small intestinal adenocarcinomas (<jats:italic>P<\/jats:italic>\u2009=\u20090.001) compared to <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010JAX<\/jats:italic><\/jats:sup> mice. Male <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010FCCC<\/jats:italic><\/jats:sup> mice had significantly greater numbers of colorectal adenomas compared to female <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010FCCC<\/jats:italic><\/jats:sup> mice (<jats:italic>P<\/jats:italic>\u2009=\u20090.0002), as did male <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010JAX<\/jats:italic><\/jats:sup> mice vs. female <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010JAX<\/jats:italic><\/jats:sup> mice (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001). These results allow us to conclude: (1) <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010FCCC<\/jats:italic><\/jats:sup> mice are unique in that they develop significantly greater numbers of colorectal adenomas and small intestinal cancers, and a significantly greater incidence of small intestinal cancers and rectal prolapse than <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010JAX<\/jats:italic><\/jats:sup> mice. (2) This study represents the first report of a significant gender difference in multiplicity of colorectal adenomas. (3) Differences between <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010FCCC<\/jats:italic><\/jats:sup> and <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010JAX<\/jats:italic><\/jats:sup> mice in currently undefined genetic modifiers may contribute to the enhanced colorectal phenotype. (4) The <jats:italic>Apc<\/jats:italic><jats:sup>+\/<jats:italic>Min\u2010FCCC<\/jats:italic><\/jats:sup> strain is highly suited for the investigation of colorectal neoplastic disease and chemoprevention studies. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.20114","type":"journal-article","created":{"date-parts":[[2005,6,6]],"date-time":"2005-06-06T02:46:38Z","timestamp":1118025998000},"page":"31-41","source":"Crossref","is-referenced-by-count":36,"title":["Generation of a unique strain of multiple intestinal neoplasia (<i>Apc<\/i><sup>+\/<i>Min\u2010FCCC<\/i><\/sup>) mice with significantly increased numbers of colorectal adenomas"],"prefix":"10.1002","volume":"44","author":[{"given":"Harry S.","family":"Cooper","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Chi L.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Coudry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique A.","family":"Gary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynette","family":"Everley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia S.","family":"Spittle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Litwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margie L.","family":"Clapper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,6,5]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199412223312507"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61155-8"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.48.1.1"},{"key":"e_1_2_7_5_2","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1016\/0016-5085(94)90408-1","article-title":"Phenotypic variability of familial adenomatous polyposis in eleven unrelated families with identical Apc gene mutation","volume":"106","author":"Giardello FM","year":"1994","journal-title":"Gastroenterology"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.43.5.675"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.45.6.829"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70478-0"},{"key":"e_1_2_7_9_2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/35094067","article-title":"Apc, signal transduction and genetic instability in colorectal cancer","volume":"1","author":"Fodde R","year":"2001","journal-title":"Nat Rev"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.10.4482"},{"key":"e_1_2_7_11_2","first-page":"1644","article-title":"Morphological and molecular process of polyp formation in Apc\n                  \u0394\/716 knockout mice","volume":"57","author":"Oshima H","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-010X(19970215)277:3<245::AID-JEZ5>3.0.CO;2-O"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2296722"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-419X(96)00041-8"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.11.5848"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203646"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.206002"},{"key":"e_1_2_7_18_2","first-page":"5413","article-title":"The CAST\/Ei strain confers significant protection against Apc (Min) intestinal polyps, independent of the resistant modifier of Min1 (Mom1) locus","volume":"62","author":"Koratkar R","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_7_19_2","first-page":"4533","article-title":"Opposite effects of modifiers of the Apc\n                  \n                     Min\n                   mutation in intestine and mammary gland","volume":"63","author":"Czarnomska A","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1350108"},{"key":"e_1_2_7_21_2","first-page":"391","article-title":"Point: From animal models to prevention of colon cancer. 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