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Blood, 1 February 2004, Vol. 103, No. 3, pp. 1050-1058. Prepublished online as a Blood First Edition Paper on October 2, 2003; DOI 10.1182/blood-2003-03-0707. This Article Full Text (PDF) All Versions of this Article: 2003-03-0707v1 103/3/1050    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Coletta, P L Articles by Markham, A. F Search for Related Content PubMed PubMed Citation Articles by Coletta, P L Articles by Markham, A. F Social Bookmarking                   What's this? Submitted March 6, 2003 Accepted September 16, 2003 Lymphodepletion in the ApcMin/+ mouse model of intestinal tumorigenesis P L Coletta*, Albrecht M Muller, Elena A Jones, Bettina Muhl, Sarah Holwell, Deborah Clarke, Josephine L Meade, Graham P Cook, Gillian Hawcroft, Frederique Ponchel, Wai K Lam, Ken A MacLennan, Mark A Hull, Constanze Bonifer, and Alexander F Markham Molecular Medicine Unit, University of Leeds, Leeds, United Kingdom Institut fur Medizinische Strahlenkunde und Zellforschung, Universitat Wuerzburg, Wurzburg, Germany * Corresponding author; email: p.l.coletta{at}leeds.ac.uk. Germline mutations in the Adenomatous polyposis coli tumour suppressor gene cause a hereditary form of intestinal tumorigenesis in both mice and man. Here we show that in ApcMin/+ mice which carry a heterozygous germline mutation at codon 850 of Apc, there is progressive loss of immature and mature thymocytes from approximately 80 days of age with complete regression of the thymus by 120 days. In addition, ApcMin/+ mice show parallel depletion of splenic NK cells, immature B cells and B progenitor cells in bone marrow due to complete loss of IL-7 dependent B cell progenitors. Using bone marrow transplantation experiments into wild-type recipients, we have shown that the capacity of transplanted ApcMin/+ bone marrow cells for T and B cell development appears normal. In contrast, although the ApcMin/+ bone marrow microenvironment supported short-term reconstitution with wild-type bone marrow, transplanted ApcMin/+ animals subsequently underwent lymphodepletion. CFU-F colony assays revealed a significant reduction in colony-forming mesenchymal progenitor cells in the bone marrow of ApcMin/+ mice compared with wild-type animals prior to the onset of lymphodepletion. This suggests that an altered bone marrow microenvironment may account for the selective lymphocyte depletion observed in this model of familial adenomatous polyposis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Frantz, J. Tillmanns, P. J. Kuhlencordt, I. Schmidt, A. Adamek, C. Dienesch, T. Thum, S. Gerondakis, G. Ertl, and J. Bauersachs Tissue-Specific Effects of the Nuclear Factor {kappa}B Subunit p50 on Myocardial Ischemia-Reperfusion Injury Am. J. Pathol., August 1, 2007; 171(2): 507 - 512. [Abstract] [Full Text] [PDF] V. P. Rao, T. Poutahidis, J. G. Fox, and S. E. Erdman Breast Cancer: Should Gastrointestinal Bacteria Be on Our Radar Screen? Cancer Res., February 1, 2007; 67(3): 847 - 850. [Abstract] [Full Text] [PDF] V. P. Rao, T. Poutahidis, Z. Ge, P. R. Nambiar, C. Boussahmain, Y. Y. Wang, B. H. Horwitz, J. G. Fox, and S. E. Erdman Innate Immune Inflammatory Response against Enteric Bacteria Helicobacter hepaticus Induces Mammary Adenocarcinoma in Mice. Cancer Res., August 1, 2006; 66(15): 7395 - 7400. [Abstract] [Full Text] [PDF] M.A. Hull, O.O. Faluyi, C.W.S. Ko, S. Holwell, D.J. Scott, R.J. Cuthbert, R. Poulsom, R. Goodlad, C. Bonifer, A.F. Markham, et al. Regulation of stromal cell cyclooxygenase-2 in the ApcMin/+ mouse model of intestinal tumorigenesis Carcinogenesis, March 1, 2006; 27(3): 382 - 391. [Abstract] [Full Text] [PDF] K. A. Mehl, J. M. Davis, J. M. Clements, F. G. Berger, M. M. Pena, and J. A. Carson Decreased intestinal polyp multiplicity is related to exercise mode and gender in ApcMin/+ mice J Appl Physiol, June 1, 2005; 98(6): 2219 - 2225. [Abstract] [Full Text] [PDF] S. E. Erdman, J. J. Sohn, V. P. Rao, P. R. Nambiar, Z. Ge, J. G. Fox, and D. B. Schauer CD4+CD25+ Regulatory Lymphocytes Induce Regression of Intestinal Tumors in ApcMin/+ Mice Cancer Res., May 15, 2005; 65(10): 3998 - 4004. [Abstract] [Full Text] [PDF]

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