Abstract
Given the importance of B lymphocytes in inflammation and immune defense against pathogens, mice transgenic for Cre under the control of Cd19 promoter (Cd19Cre/+ mice) have been widely used to specifically investigate the role of loxP-flanked genes in B cell development/function. However, impacts of expression/insertion of the Cre transgene on the phenotype and function of B cells have not been carefully studied. Here, we show that the number of marginal zone B and B1a cells was selectively reduced in Cd19Cre/+ mice, while B cell development in the bone marrow and total numbers of peripheral B cells were comparable between Cd19Cre/+ and wild type C57BL/6 mice. Notably, humoral responses to both T cell-dependent and independent antigens were significantly increased in Cd19Cre/+ mice. We speculate that these differences are mainly attributable to reduced surface CD19 levels caused by integration of the Cre-expressing cassette that inactivates one Cd19 allele. Moreover, our literature survey showed that expression of Cd19Cre/+ alone may affect the development/progression of inflammatory and anti-infectious responses. Thus, our results have important implications for the design and interpretation of results on gene functions specifically targeted in B cells in the Cd19Cre/+ mouse strain, for instance, in the context of (auto) inflammatory/infectious diseases.
Highlights
The Cre/loxP recombination system has been widely used to edit mammalian genomes in genetic and biomedical studies
Given that CD19 acts as a B-cell receptor (BCR) co-receptor, and may regulate
Bcell development [22–25], we performed a detailed comparison on the B cell development and phenotype in WT (Cd19+/+ ) vs. Cd19Cre/+ mice
Summary
The Cre/loxP recombination system has been widely used to edit mammalian genomes in genetic and biomedical studies. Upon recognizing the 34-bp-long loxP motif inserted at defined positions of the genome, the recombinase Cre and efficiently drives the recombination of DNA segments flanked by two loxP recognition sites (‘floxed’ locus) [1]. The regulation of Cre expression with inducible or cell/tissue-specific promoters represents an elegant and powerful approach to precisely interrogate the function of genes that have been inactivated or activated in a spatially and temporally specific fashion [2]. Given that the mammalian genome comprises many cryptic/pseudo loxP sites, for instance, at an estimated frequency of 1.2 per megabase in the mouse genome, the mere expression of Cre is potentially toxic to cells and may result in reduced proliferation, aberrant DNA recombination, and chromosomal defects [7–11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
