TCR deep sequencing of transgenic RAG-1-deficient mice reveals endogenous TCR recombination: a cause for caution

Journal Publication ResearchOnline@JCU
McGuire, Helen M.;Watkins, Thomas S.;Field, Matthew;Taylor, Sarah;Yasuyama, Nao;Farmer, Andrew;Miles, John J.;Fazekas de St. Groth, Barbara
Matt Field
Abstract

The utility of T-cell receptor (TCR) transgenic mice in medical research has been considerable, with applications ranging from basic biology all the way to translational and clinical investigations. Crossing of TCR transgenic mice with either recombination-activating gene (RAG)-1 or RAG-2 knockouts is frequently used to generate mice with a monoclonal T-cell repertoire. However, low level productive TCR rearrangement has been reported in RAG-deficient mice expressing transgenic TCRs. Using deep sequencing, we set out to directly examine and quantify the presence of these endogenous TCRs. Our demonstration that functional nontransgenic TCRs are present in nonmanipulated mice has wide reaching ramifications worthy of critical consideration.

Journal

Immunology and Cell Biology

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Volume

96

ISBN/ISSN

1440-1711

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Issue

6

Pages Count

4

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Publisher

Wiley

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EISSN

N/A

DOI

10.1111/imcb.12033