Tissue-specific sensitivity to AID expression in transgenic mouse models

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

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)150-158
Number of pages9
JournalGene
Volume377
Issue number1-2
DOIs
StatePublished - Aug 1 2006

Keywords

  • Activation-induced deaminase
  • Animal model
  • Ectopic expression
  • Thymic lymphomas

ASJC Scopus subject areas

  • Genetics

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  • Cite this

    Rucci, F., Cattaneo, L., Marrella, V., Sacco, M. G., Sobacchi, C., Lucchini, F., Nicola, S., Della Bella, S., Villa, M. L., Imberti, L., Gentili, F., Montagna, C., Tiveron, C., Tatangelo, L., Facchetti, F., Vezzoni, P., & Villa, A. (2006). Tissue-specific sensitivity to AID expression in transgenic mouse models. Gene, 377(1-2), 150-158. https://doi.org/10.1016/j.gene.2006.03.024