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Generation of immunodeficient rats with Rag1 and Il2rg gene deletions and human tissue grafting models.

Authors: Ménoret, Séverine  Ouisse, Laure-Hélène  Tesson, Laurent  Delbos, Frédéric  Garnier, Delphine  Remy, Séverine  Usal, Claire  Concordet, Jean-Paul  Giovannangeli, Carine  Chenouard, Vanessa  Brusselle, Lucas  Merieau, Emmanuel  Nerrière-Daguin, Véronique  Duteille, Franck  Bellier-Waast, Frédérique  Fraichard, Alexandre  Nguyen, Tuan H  Anegon, Ignacio 
Citation: Ménoret S, etal., Transplantation. 2018 Apr 24. doi: 10.1097/TP.0000000000002251.
Pubmed: (View Article at PubMed) PMID:29688994
DOI: Full-text: DOI:10.1097/TP.0000000000002251


BACKGROUND: Immunodeficient mice are invaluable tools to analyze the long-term effects of potentially immunogenic molecules in the absence of adaptive immune responses. Nevertheless, there are models and experimental situations that would beneficiate of larger immunodeficient recipients. Rats are ideally suited to perform experiments in which larger size is needed and are still a small animal model suitable for rodent facilities. Additionally, rats reproduce certain human diseases better than mice, such as ankylosing spondylitis and Duchenne disease and these disease models would greatly benefit of immunodeficient rats to test different immunogenic treatments.
METHODS: We describe the generation of Il2rg-deficient rats and their crossing with previously described Rag1-deficient rats to generate double-mutant RRG animals.
RESULTS: As compared to Rag1-deficient rats, Il2rg-deficient rats were more immunodeficient since partially lacked not only T and B cells but also NK cells. RRG animals showed a more profound immunossuppressed phenotype since they displayed undetectable levels of T, B and NK cells. Similarly, all immunoglobulin isotypes in sera were decreased in Rag1 or Il2rg-deficient rats and undetectable in RRG animals. Rag1 or Il2rg-deficient rats rejected allogeneic skin transplants and human tumors whereas RRG animals not only accepted allogeneic rat skin but also xenogeneic human tumors, skin and hepatocytes. Immune humanization of RRG animals was unsuccessful.
CONCLUSION: Thus, immunodeficient RRG animals are useful recipients for long term studies in which immune responses could be an obstacle, including tissue humanization of different tissues.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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CRRD Object Information
CRRD ID: 13628403
Created: 2018-06-19
Species: All species
Last Modified: 2018-06-19
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.