Lyz2 -Cre-Mediated Genetic Deletion of Septin7 Reveals a Role of Septins in Macrophage Cytokinesis and Kras -Driven Tumorigenesis
By crossing -floxed mice with -Cre mice carrying the Cre recombinase inserted in the Lysozyme-M ( ) gene locus we aimed the specific deletion of septin7 in myeloid cells, such as monocytes, macrophages and granulocytes. : Cre mice show no alterations in the myeloid compartment. -deleted macrophages...
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Veröffentlicht in: | Frontiers in cell and developmental biology 2022-01, Vol.9, p.795798-795798 |
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Sprache: | eng |
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Zusammenfassung: | By crossing
-floxed mice with
-Cre mice carrying the Cre recombinase inserted in the Lysozyme-M (
) gene locus we aimed the specific deletion of septin7 in myeloid cells, such as monocytes, macrophages and granulocytes.
:
Cre mice show no alterations in the myeloid compartment.
-deleted macrophages (BMDMs) were isolated and analyzed. The lack of Septin7 expression was confirmed and a constitutive double-nucleation was detected in Septin7-deficient BMDMs indicating a defect in macrophage cytokinesis. However, phagocytic function of macrophages as judged by uptake of labelled
particles and LPS-stimulated macrophage activation as judged by induction of TNF mRNA expression and TNF secretion were not compromised. In addition to myeloid cells, Lyz2-Cre is also active in type II pneumocytes (AT2 cells). We monitored lung adenocarcinoma formation in these mice by crossing them with the conditional knock-in
-LSL-G12D allele. Interestingly, we found that control mice without septin7 depletion die after 3-5 weeks, while the Septin7-deficient animals survived 11 weeks or even longer. Control mice sacrificed in the age of 4 weeks display a bronchiolo-alveolar hyperplasia with multiple adenomas, whereas the Septin7-deficient animals of the same age are normal or show only a weak multifocal brochiolo-alveolar hyperplasia. Our findings indicate an essential role of Septin7 in macrophage cytokinesis but not in macrophage function. Furthermore, septin7 seems absolutely essential for oncogenic
-driven lung tumorigenesis making it a potential target for anti-tumor interventions. |
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ISSN: | 2296-634X 2296-634X |
DOI: | 10.3389/fcell.2021.795798 |