The Cre/loxP system is extensively utilized to pinpoint gene functions in specific cell types or developmental stages, typically without major disturbance to the host's genome. However, we found that the random insertion of the Mrp8-cre transgene significantly promotes the host's innate immune response. This effect is characterized by elevated susceptibility to cartilage antibody-induced arthritis, likely due to interference with genes near the insertion site. These findings underscore the potential biological disturbances caused by random transgene integration, and the necessity for stringent control strategies to avoid biased interpretations when using Cre-conditional strains.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41435-024-00313-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The need for Cre-loci controls in conditional mouse experiments: Mrp8-cre transgene predisposes mice to antibody-induced arthritis.
Genes Immun
December 2024
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
The Cre/loxP system is extensively utilized to pinpoint gene functions in specific cell types or developmental stages, typically without major disturbance to the host's genome. However, we found that the random insertion of the Mrp8-cre transgene significantly promotes the host's innate immune response. This effect is characterized by elevated susceptibility to cartilage antibody-induced arthritis, likely due to interference with genes near the insertion site.
View Article and Find Full Text PDFIdentification of the Transgene Integration Site and Host Genome Changes in MRP8-Cre/ires-EGFP Transgenic Mice by Targeted Locus Amplification.
Front Immunol
April 2022
Department of Pathology, Dana-Farber/Harvard Cancer Center, Harvard Medical School, Boston, MA, United States.
The MRP8-Cre-ires/EGFP transgenic mouse (Mrp8cre, on C57BL/6J genetic background) is popular in immunological and hematological research for specifically expressing Cre recombinase and an EGFP reporter in neutrophils. It is often crossed with other transgenic lines carrying -flanked genes to achieve restricted gene knockout in neutrophils. However, due to the way in which the line was created, basic knowledge about the MRP8-Cre-ires/EGFP transgene in the host genome, such as its integration site(s) and flanking sequences, remains largely unknown, hampering robust experimental design and data interpretation.
View Article and Find Full Text PDFLineage-Specific Analysis of Syk Function in Autoantibody-Induced Arthritis.
Front Immunol
May 2019
Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary.
Autoantibody production and autoantibody-mediated inflammation are hallmarks of a number of autoimmune diseases. The K/BxN serum-transfer arthritis is one of the most widely used models of the effector phase of autoantibody-induced pathology. Several hematopoietic lineages including neutrophils, platelets, and mast cells have been proposed to contribute to inflammation and tissue damage in this model.
View Article and Find Full Text PDFEndoplasmic Reticulum Stress of Neutrophils Is Required for Ischemia/Reperfusion-Induced Acute Lung Injury.
J Immunol
November 2015
Department of Anesthesiology, School of Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China;
Diverse clinical factors, including intestinal ischemia, contribute to acute lung injury (ALI), which has up to a 40% mortality rate. During the development of lung injury an immune response is elicited that exacerbates the lung insult. Neutrophils have been well studied in mediating the pulmonary insults through an assortment of mechanisms, such as release of granule contents and production of proinflammatory cytokines due to the overactivation of complement and cytokines.
View Article and Find Full Text PDFWant 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!