Humanized Rodent Platform

Research “from bench to bedside” requires a first Proof of Concept in a disease-relevant model. However, biologics targeting the immune system such as monoclonal antibodies and recombinant proteins are often species-specific and cannot be tested in classical animal models. To circumvent this hurdle, IGO/WP1-Project P2 aims at setting up humanized mouse (NSG) and rat models, i.e. immunodeficient animals grafted with human hematopoietic precursor cells for the generation of a stable human immune system.
Humanization of rats is a novel tool, based on the inactivation of the IgM (Menoret et al, Eur J Immunol 40, 2932, 2010), RAG and IL2Rg genes with TALEN nucleases, as recently described by IGO members (Tesson et al. Nat. Biotechnol. 2010)(Ménoret et al, FASEB J. 2012, in press).
The humanized rodent platform is used for the preclinical evaluation of molecules and therapeutic strategies identified/developed by IGO participants, which modify immune responses by promoting or dampening immune tolerance, finding direct applications in organ, cell and gene transplantation or by promoting anti-cancer immune responses.

Mice are housed and integrated in the mouse facility of the IRTUN that combines a space for animal breeding, a A2 laboratory and direct access to the irradiation facility.

Rats are housed in the Transgenesis Rats PlatForm – NANTES http://www.tgr.nantes.inserm.fr/ located in the Transplantation Institute of Nantes and http://www.itun.nantes.inserm.fr/

Your contacts: Fabienne Haspot and Véronique Daguin,

INSERM UMR 1064, Nantes - fabienne.haspot@univ-nantes.fr