Lymphodepletion in the ApcMin/+ mouse model of intestinal tumorigenesis
Germ line mutations in the Adenomatous polyposis coli tumor 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 germ line mutation at codon 850 of Apc, there is progressive loss of immature and matur...
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| Veröffentlicht in: | Blood 2004-02, Vol.103 (3), p.1050-1058 |
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| creator | Coletta, P. Louise Müller, Albrecht M. Jones, Elena A. Mühl, Bettina Holwell, Sarah Clarke, Deborah Meade, Josephine L. Cook, Graham P. Hawcroft, Gillian Ponchel, Frederique Lam, Wai K. MacLennan, Ken A. Hull, Mark A. Bonifer, Constanze Markham, Alexander F. |
| description | Germ line mutations in the Adenomatous polyposis coli tumor 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 germ line 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 natural killer (NK) cells, immature B cells, and B progenitor cells in bone marrow due to complete loss of interleukin 7 (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, ApcMin/+ animals that received transplants subsequently underwent lymphodepletion. Fibroblast colony-forming unit (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. (Blood. 2004;103:1050-1058) |
| doi_str_mv | 10.1182/blood-2003-03-0707 |
| format | Article |
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Louise ; Müller, Albrecht M. ; Jones, Elena A. ; Mühl, Bettina ; Holwell, Sarah ; Clarke, Deborah ; Meade, Josephine L. ; Cook, Graham P. ; Hawcroft, Gillian ; Ponchel, Frederique ; Lam, Wai K. ; MacLennan, Ken A. ; Hull, Mark A. ; Bonifer, Constanze ; Markham, Alexander F.</creator><creatorcontrib>Coletta, P. Louise ; Müller, Albrecht M. ; Jones, Elena A. ; Mühl, Bettina ; Holwell, Sarah ; Clarke, Deborah ; Meade, Josephine L. ; Cook, Graham P. ; Hawcroft, Gillian ; Ponchel, Frederique ; Lam, Wai K. ; MacLennan, Ken A. ; Hull, Mark A. ; Bonifer, Constanze ; Markham, Alexander F.</creatorcontrib><description>Germ line mutations in the Adenomatous polyposis coli tumor 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 germ line 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 natural killer (NK) cells, immature B cells, and B progenitor cells in bone marrow due to complete loss of interleukin 7 (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, ApcMin/+ animals that received transplants subsequently underwent lymphodepletion. Fibroblast colony-forming unit (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. (Blood. 2004;103:1050-1058)</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2003-03-0707</identifier><identifier>PMID: 14525778</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Adenomatous Polyposis Coli - genetics ; Adenomatous Polyposis Coli - immunology ; Adenomatous Polyposis Coli - pathology ; Animals ; Atrophy ; Biological and medical sciences ; Bone Marrow Transplantation ; Disease Models, Animal ; Female ; Gastroenterology. Liver. Pancreas. 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Anus ; Thymus Gland - immunology ; Thymus Gland - pathology ; Tumors</subject><ispartof>Blood, 2004-02, Vol.103 (3), p.1050-1058</ispartof><rights>2004 American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2737-e9fba6010566c87711e708c5e015f9611ae155397868e2b16925b29fdbbb5d023</citedby><cites>FETCH-LOGICAL-c2737-e9fba6010566c87711e708c5e015f9611ae155397868e2b16925b29fdbbb5d023</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15883638$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14525778$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Coletta, P. Louise</creatorcontrib><creatorcontrib>Müller, Albrecht M.</creatorcontrib><creatorcontrib>Jones, Elena A.</creatorcontrib><creatorcontrib>Mühl, Bettina</creatorcontrib><creatorcontrib>Holwell, Sarah</creatorcontrib><creatorcontrib>Clarke, Deborah</creatorcontrib><creatorcontrib>Meade, Josephine L.</creatorcontrib><creatorcontrib>Cook, Graham P.</creatorcontrib><creatorcontrib>Hawcroft, Gillian</creatorcontrib><creatorcontrib>Ponchel, Frederique</creatorcontrib><creatorcontrib>Lam, Wai K.</creatorcontrib><creatorcontrib>MacLennan, Ken A.</creatorcontrib><creatorcontrib>Hull, Mark A.</creatorcontrib><creatorcontrib>Bonifer, Constanze</creatorcontrib><creatorcontrib>Markham, Alexander F.</creatorcontrib><title>Lymphodepletion in the ApcMin/+ mouse model of intestinal tumorigenesis</title><title>Blood</title><addtitle>Blood</addtitle><description>Germ line mutations in the Adenomatous polyposis coli tumor 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 germ line 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 natural killer (NK) cells, immature B cells, and B progenitor cells in bone marrow due to complete loss of interleukin 7 (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, ApcMin/+ animals that received transplants subsequently underwent lymphodepletion. Fibroblast colony-forming unit (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. (Blood. 2004;103:1050-1058)</description><subject>Adenomatous Polyposis Coli - genetics</subject><subject>Adenomatous Polyposis Coli - immunology</subject><subject>Adenomatous Polyposis Coli - pathology</subject><subject>Animals</subject><subject>Atrophy</subject><subject>Biological and medical sciences</subject><subject>Bone Marrow Transplantation</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Genes, APC</subject><subject>Germ-Line Mutation</subject><subject>Hematopoiesis</subject><subject>Humans</subject><subject>Lymph Nodes - immunology</subject><subject>Lymph Nodes - pathology</subject><subject>Lymphocyte Subsets - immunology</subject><subject>Lymphocyte Subsets - pathology</subject><subject>Lymphopenia - genetics</subject><subject>Lymphopenia - immunology</subject><subject>Lymphopenia - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Mutant Strains</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. 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Louise</creator><creator>Müller, Albrecht M.</creator><creator>Jones, Elena A.</creator><creator>Mühl, Bettina</creator><creator>Holwell, Sarah</creator><creator>Clarke, Deborah</creator><creator>Meade, Josephine L.</creator><creator>Cook, Graham P.</creator><creator>Hawcroft, Gillian</creator><creator>Ponchel, Frederique</creator><creator>Lam, Wai K.</creator><creator>MacLennan, Ken A.</creator><creator>Hull, Mark A.</creator><creator>Bonifer, Constanze</creator><creator>Markham, Alexander F.</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20040201</creationdate><title>Lymphodepletion in the ApcMin/+ mouse model of intestinal tumorigenesis</title><author>Coletta, P. Louise ; Müller, Albrecht M. ; Jones, Elena A. ; Mühl, Bettina ; Holwell, Sarah ; Clarke, Deborah ; Meade, Josephine L. ; Cook, Graham P. ; Hawcroft, Gillian ; Ponchel, Frederique ; Lam, Wai K. ; MacLennan, Ken A. ; Hull, Mark A. ; Bonifer, Constanze ; Markham, Alexander F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2737-e9fba6010566c87711e708c5e015f9611ae155397868e2b16925b29fdbbb5d023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adenomatous Polyposis Coli - genetics</topic><topic>Adenomatous Polyposis Coli - immunology</topic><topic>Adenomatous Polyposis Coli - pathology</topic><topic>Animals</topic><topic>Atrophy</topic><topic>Biological and medical sciences</topic><topic>Bone Marrow Transplantation</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Genes, APC</topic><topic>Germ-Line Mutation</topic><topic>Hematopoiesis</topic><topic>Humans</topic><topic>Lymph Nodes - immunology</topic><topic>Lymph Nodes - pathology</topic><topic>Lymphocyte Subsets - immunology</topic><topic>Lymphocyte Subsets - pathology</topic><topic>Lymphopenia - genetics</topic><topic>Lymphopenia - immunology</topic><topic>Lymphopenia - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Mutant Strains</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Thymus Gland - immunology</topic><topic>Thymus Gland - pathology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Coletta, P. Louise</creatorcontrib><creatorcontrib>Müller, Albrecht M.</creatorcontrib><creatorcontrib>Jones, Elena A.</creatorcontrib><creatorcontrib>Mühl, Bettina</creatorcontrib><creatorcontrib>Holwell, Sarah</creatorcontrib><creatorcontrib>Clarke, Deborah</creatorcontrib><creatorcontrib>Meade, Josephine L.</creatorcontrib><creatorcontrib>Cook, Graham P.</creatorcontrib><creatorcontrib>Hawcroft, Gillian</creatorcontrib><creatorcontrib>Ponchel, Frederique</creatorcontrib><creatorcontrib>Lam, Wai K.</creatorcontrib><creatorcontrib>MacLennan, Ken A.</creatorcontrib><creatorcontrib>Hull, Mark A.</creatorcontrib><creatorcontrib>Bonifer, Constanze</creatorcontrib><creatorcontrib>Markham, Alexander F.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Coletta, P. Louise</au><au>Müller, Albrecht M.</au><au>Jones, Elena A.</au><au>Mühl, Bettina</au><au>Holwell, Sarah</au><au>Clarke, Deborah</au><au>Meade, Josephine L.</au><au>Cook, Graham P.</au><au>Hawcroft, Gillian</au><au>Ponchel, Frederique</au><au>Lam, Wai K.</au><au>MacLennan, Ken A.</au><au>Hull, Mark A.</au><au>Bonifer, Constanze</au><au>Markham, Alexander F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lymphodepletion in the ApcMin/+ mouse model of intestinal tumorigenesis</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2004-02-01</date><risdate>2004</risdate><volume>103</volume><issue>3</issue><spage>1050</spage><epage>1058</epage><pages>1050-1058</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Germ line mutations in the Adenomatous polyposis coli tumor 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 germ line 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 natural killer (NK) cells, immature B cells, and B progenitor cells in bone marrow due to complete loss of interleukin 7 (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, ApcMin/+ animals that received transplants subsequently underwent lymphodepletion. Fibroblast colony-forming unit (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. (Blood. 2004;103:1050-1058)</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>14525778</pmid><doi>10.1182/blood-2003-03-0707</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenomatous Polyposis Coli - genetics Adenomatous Polyposis Coli - immunology Adenomatous Polyposis Coli - pathology Animals Atrophy Biological and medical sciences Bone Marrow Transplantation Disease Models, Animal Female Gastroenterology. Liver. Pancreas. Abdomen Genes, APC Germ-Line Mutation Hematopoiesis Humans Lymph Nodes - immunology Lymph Nodes - pathology Lymphocyte Subsets - immunology Lymphocyte Subsets - pathology Lymphopenia - genetics Lymphopenia - immunology Lymphopenia - pathology Male Medical sciences Mice Mice, Inbred C57BL Mice, Mutant Strains Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Thymus Gland - immunology Thymus Gland - pathology Tumors |
| title | Lymphodepletion in the ApcMin/+ mouse model of intestinal tumorigenesis |
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