Widespread discrepancy in Nnt genotypes and genetic backgrounds complicates granzyme A and other knockout mouse studies.

ABSTRACT: Granzyme A (GZMA) is a serine protease secreted by cytotoxic lymphocytes, with Gzma^-/- mouse studies having informed our understanding of GZMA's physiological function. We show herein that Gzma^-/- mice have a mixed C57BL/6J and C57BL/6N genetic background and retain the full-length nicotinamide nucleotide transhydrogenase (Nnt) gene, whereas Nnt is truncated in C57BL/6J mice. Chikungunya viral arthritis was substantially ameliorated in Gzma^-/- mice; however, the presence of Nnt and the C57BL/6N background, rather than loss of GZMA expression, was responsible for this phenotype. A new CRISPR active site mutant C57BL/6J Gzma^S211A mouse provided the first insights into GZMA's bioactivity free of backg

SUBMITTER: Rawle DJ 

PROVIDER: S-EPMC8816380 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature