Lymphodepletion in the ApcMin/+ mouse model of intestinal tumorigenesis
| Autor: | Mark A. Hull, Alexander F. Markham, Bettina Mühl, P. Louise Coletta, Josephine L. Meade, Deborah Clarke, Sarah Holwell, Constanze Bonifer, Graham P. Cook, Frederique Ponchel, Gillian Hawcroft, Albrecht M. Müller, Elena Jones, Wai K. Lam, Ken A. MacLennan |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Pathology medicine.medical_specialty Genes APC Tumor suppressor gene Adenomatous polyposis coli Immunology Thymus Gland medicine.disease_cause Biochemistry Familial adenomatous polyposis Mice Lymphopenia medicine Animals Humans Progenitor cell Germ-Line Mutation Bone Marrow Transplantation biology Interleukin Cell Biology Hematology medicine.disease Lymphocyte Subsets Mice Mutant Strains Hematopoiesis Mice Inbred C57BL Haematopoiesis Disease Models Animal medicine.anatomical_structure Adenomatous Polyposis Coli biology.protein Cancer research Female Bone marrow Lymph Nodes Atrophy Carcinogenesis |
| Zdroj: | Blood. 103(3) |
| ISSN: | 0006-4971 |
| Popis: | 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) |
| Databáze: | OpenAIRE |
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