A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_sessioniq3nimv229g3i7ip1kkell2i8l984q4q): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests

Filename: helpers/my_audit_helper.php

Line Number: 143

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 994
Function: getPubMedXML

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3134
Function: GetPubMedArticleOutput_2016

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

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

AI Article Synopsis

  • Granzyme A (GZMA) is a protease secreted by cytotoxic lymphocytes, and research on mice with mixed genetic backgrounds has helped clarify its role, specifically how it is affected by genetic variations between C57BL/6J and C57BL/6N strains.
  • Mice with a C57BL/6N background showed significant improvements in chikungunya viral arthritis, linking this positive effect to the presence of specific genetic factors rather than the expression of GZMA.
  • Analyzing data from the Sequence Read Archive uncovered inconsistencies in the genetic background of many studies using C57BL/6J mice, suggesting that these background issues could skew results in various research areas.

Article Abstract

Granzyme A (GZMA) is a serine protease secreted by cytotoxic lymphocytes, with mouse studies having informed our understanding of GZMA's physiological function. We show herein that mice have a mixed C57BL/6J and C57BL/6N genetic background and retain the full-length nicotinamide nucleotide transhydrogenase () gene, whereas is truncated in C57BL/6J mice. Chikungunya viral arthritis was substantially ameliorated in mice; however, the presence of and the C57BL/6N background, rather than loss of GZMA expression, was responsible for this phenotype. A new CRISPR active site mutant C57BL/6J mouse provided the first insights into GZMA's bioactivity free of background issues, with circulating proteolytically active GZMA promoting immune-stimulating and pro-inflammatory signatures. Remarkably, k-mer mining of the Sequence Read Archive illustrated that ≈27% of Run Accessions and ≈38% of BioProjects listing C57BL/6J as the mouse strain had sequencing reads inconsistent with a C57BL/6J genetic background. and C57BL/6N background issues have clearly complicated our understanding of GZMA and may similarly have influenced studies across a broad range of fields.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8816380PMC
http://dx.doi.org/10.7554/eLife.70207DOI Listing

Publication Analysis

Top Keywords

mouse studies
8
genetic background
8
c57bl/6n background
8
c57bl/6j mouse
8
background issues
8
c57bl/6j
5
background
5
widespread discrepancy
4
discrepancy genotypes
4
genotypes genetic
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!