{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T04:55:14Z","timestamp":1764996914401},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,12,1]],"date-time":"2011-12-01T00:00:00Z","timestamp":1322697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK059911","P01 DK071176"],"award-info":[{"award-number":["R01 DK059911","P01 DK071176"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. pediatr. gastroenterol. nutr."],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective:<\/jats:title><jats:p>P\u2010glycoprotein (P\u2010gp), the functional product of the multidrug resistance gene (<jats:italic>MDR<\/jats:italic>), is a transmembrane protein that extrudes substrates from the intracellular environment. P\u2010gp is expressed on the apical surface of epithelial cells and on cells from the hematopoietic lineage. Human <jats:italic>MDR<\/jats:italic> polymorphisms have been associated with the increased risk of inflammatory bowel disease, and FVB\/N animals deficient in <jats:italic>mdr1a<\/jats:italic> expression develop spontaneous colitis. Previous studies using adult bone marrow chimeras indicated that colitis development in this animal model was contingent on P\u2010gp deficiency in radiation\u2010resistant epithelial cells; however, the use of adult animals may mask the role of hematopoietic immune cells in colitis initiation, due to preexisting epithelial abnormalities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and Methods:<\/jats:title><jats:p>To assess the importance of P\u2010gp expression in intestinal epithelial and hematopoietic\u2010derived cells on colitis induction in FVB.<jats:italic>mdr1a<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> animals, we developed a neonatal model of bone marrow reconstitution. FVB\/N and FVB.<jats:italic>mdr1a<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> adult and neonatal animals were lethally irradiated and reconstituted with bone marrow from FVB\/N or FVB.<jats:italic>mdr1a<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> donors. Animals were observed for 20 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Adult FVB\/N animals deficient in P\u2010gp expression in hematopoietically derived immune cells developed colitis similar to adult animals deficient in P\u2010gp expression in radiation\u2010resistant epithelial\/stromal cells. Neonatal animals deficient in P\u2010gp expression in hematopoietically derived immune cells developed a more histologically significant colitis than those deficient in P\u2010gp expression in epithelial tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>The use of a neonatal model of bone marrow reconstitution has revealed a critical role for P\u2010gp expression in hematopoietically derived immune cells in colitis development in the FVB.<jats:italic>mdr1a<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> model.<\/jats:p><\/jats:sec>","DOI":"10.1097\/mpg.0b013e31822860f1","type":"journal-article","created":{"date-parts":[[2011,6,16]],"date-time":"2011-06-16T21:05:09Z","timestamp":1308258309000},"page":"666-673","source":"Crossref","is-referenced-by-count":7,"title":["Critical Role for P\u2010Glycoprotein Expression in Hematopoietic Cells in the FVB.<i>Mdr1a<\/i><sup><i>\u2212\/\u2212<\/i><\/sup> Model of Colitis"],"prefix":"10.1002","volume":"53","author":[{"given":"Elizabeth M.","family":"Staley","sequence":"first","affiliation":[{"name":"Department of Microbiology University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reed A.","family":"Dimmitt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trenton R.","family":"Schoeb","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott M.","family":"Tanner","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin G.","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Alabama at 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