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. 1995 Sep 1;14(17):4230–4239. doi: 10.1002/j.1460-2075.1995.tb00097.x

Granzyme A-deficient mice retain potent cell-mediated cytotoxicity.

K Ebnet 1, M Hausmann 1, F Lehmann-Grube 1, A Müllbacher 1, M Kopf 1, M Lamers 1, M M Simon 1
PMCID: PMC394506  PMID: 7556064

Abstract

Granzyme A, a granule-associated serine proteinase of activated cytotoxic T cells and natural killer cells, has been reported to play a critical role in DNA fragmentation of target cells. To address the question of the biological role of granzyme A, we have now generated a granzyme A-deficient mouse mutant by homologous recombination. Western blot analysis, enzyme assays and reverse transcription-PCR confirmed the absence of granzyme A in activated T cells. In addition, deletion of granzyme A does not alter the expression patterns of other granule components, such as granzymes B-G and perforin. Granzyme A-deficient mice are healthy and show normal hematopoietic development. Most notably, their in vitro- and ex vivo-derived cytotoxic T cells and natural killer cells are indistinguishable from those of normal mice in causing membrane disruption, apoptosis and DNA fragmentation in target cells. Furthermore, granzyme A-deficient mice readily recover from both lymphocytic choriomeningitis virus and Listeria monocytogenes infections and eradicate syngeneic tumors with kinetics similar to the wild-type strain. These results demonstrate that granzyme A does not play a primary role in cell-mediated cytotoxicity, as has been assumed previously.

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Selected References

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