| First Author | Eckert N | Year | 2020 |
| Journal | J Leukoc Biol | Volume | 107 |
| Issue | 6 | Pages | 1155-1166 |
| PubMed ID | 31841228 | Mgi Jnum | J:298112 |
| Mgi Id | MGI:6471188 | Doi | 10.1002/JLB.2MA1119-300R |
| Citation | Eckert N, et al. (2020) B cell hyperactivation in an Ackr4-deficient mouse strain is not caused by lack of ACKR4 expression. J Leukoc Biol 107(6):1155-1166 |
| abstractText | The majority of genetically modified C57BL/6 mice contain congenic passenger DNA around the targeted gene locus as they were generated from 129-derived embryonic stem cells (ESCs) with subsequent backcrossing to the C57BL/6 genetic background. When studying the role of atypical chemokine receptor 4 (ACKR4) in the immune system, we realized that the two available Ackr4-deficient mouse strains (Ackr4(-/-) and Ackr4(GFP/GFP) ) show profoundly different phenotypes: Compared to wild-type and Ackr4(GFP/GFP) mice, Ackr4(-/-) mice show a strong accumulation of plasma blasts in mesenteric lymph node and spleen as well as increased B cell proliferation after in vitro activation. This phenotype was maintained after further backcrossing to C57BL/6 mice and was even present in heterozygous Ackr4(+/-) animals, suggesting that a gene variant on the targeted chromosome might cause this phenotype. Exome sequencing revealed that a region of approximately 20 Mbp around the Ackr4 locus on chromosome 9 still originates from the 129 background based on high variant density observed. In activated Ackr4(-/-) and Ackr4(GFP/GFP) B cells, transcripts of genes around the Ackr4 locus were equally deregulated compared to C57BL/6 B cells, whereas increased expression of IL-6 was selectively observed in B cells of Ackr4(-/-) mice. Because the gene encoding for IL-6 is placed on chromosome 5 these findings suggest that passenger DNA around the Ackr4 locus has an indirect effect on B cell activation and IL-6 production. Results of the present study should not only lead to the reinterpretation of data from earlier studies using Ackr4(-/-) mice but should remind the scientific community about the limitations of mouse models using mice created by gene-targeting of nonsyngeneic ESCs. |
