| Tissue-specific sensitivity to AID expression in transgenic mouse models. | |
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MedLine Citation:
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PMID: 16787714 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation-induced cytidine deaminase (AID), an enzyme with homology to members of the APOBEC family, is involved in somatic hypermutation (SHM) of immunoglobulin (Ig) genes, either by direct deamination of DNA or by an indirect action through its putative RNA editing activity. AID is able to mutate both Ig-like reporter constructs and selected non-Ig genes in normal B cells and in other cells when ectopically overexpressed in mammalian cells and transgenic mice. However, in spite of the fact that in these transgenic animals AID activity was driven by an ubiquitous promoter, only T lymphomas and lung adenomas occurred. In the present work, we constructed three sets of transgenic mice in which AID was under the control of lck, HTLV-I and MMTV promoters, respectively. The lck/AID mice developed thymic lymphomas with variable but high efficiency, while no tumor was detected in HTLV-I/AID mice after two years of monitoring. Four MMTV/AID founder mice died with an atypical clinical picture, although no mammary tumor was found. These findings suggest that additional factors, present in thymocytes but not in other tissues or in lymphoid cells at different stages of differentiation, are needed for AID to fully manifest its tumorigenic potential in mouse. Alternatively, the display of full AID mutagenic and transforming activity could be related to the existence of physiologic DSBs which occur in both thymocytes and switching B cells. |
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Authors:
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Francesca Rucci; Leonardo Cattaneo; Veronica Marrella; Maria Grazia Sacco; Cristina Sobacchi; Franco Lucchini; Stefania Nicola; Silvia Della Bella; Maria Luisa Villa; Luisa Imberti; Francesca Gentili; Cristina Montagna; Cecilia Tiveron; Laura Tatangelo; Fabio Facchetti; Paolo Vezzoni; Anna Villa |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-05-03 |
Journal Detail:
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Title: Gene Volume: 377 ISSN: 0378-1119 ISO Abbreviation: Gene Publication Date: 2006 Aug |
Date Detail:
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Created Date: 2006-07-21 Completed Date: 2006-09-11 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 7706761 Medline TA: Gene Country: Netherlands |
Other Details:
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Languages: eng Pagination: 150-8 Citation Subset: IM |
Affiliation:
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Human Genome Department, Istituto di Tecnologie Biomediche, CNR, Segrate (MI), Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence Cell Differentiation Cell Transformation, Neoplastic Cytidine Deaminase / genetics*, metabolism* DNA, Complementary / genetics DNA-Binding Proteins / genetics Female Gene Expression Genes, T-Cell Receptor beta Genes, myc Genes, p53 Human T-lymphotropic virus 1 / genetics Kidney / enzymology, pathology Liver / enzymology, pathology Lymph Nodes / enzymology, pathology Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics Mammary Glands, Animal / enzymology, pathology Mammary Tumor Virus, Mouse / genetics Mice Mice, Transgenic Mutation Promoter Regions, Genetic T-Lymphocytes / enzymology, immunology, pathology Tissue Distribution |
| Chemical | |
Reg. No./Substance:
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0/DNA, Complementary; 0/DNA-Binding Proteins; 0/Rag2 protein, mouse; EC 2.7.10.2/Lymphocyte Specific Protein Tyrosine Kinase p56(lck); EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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