By crossing septin7-floxed mice with Lyz2-Cre mice carrying the Cre recombinase inserted
in the Lysozyme-M (Lyz2) gene locus we aimed the specific deletion of septin7 in myeloid
cells, such as monocytes, macrophages and granulocytes. Septin7flox/flox:Lyz2-Cre mice
show no alterations in the myeloid compartment. Septin7-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 E. coli 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 Kras-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 Kras-driven lung tumorigenesis making it a potential
target for anti-tumor interventions.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84515 |
| Date | 03 April 2023 |
| Creators | Menon, Manoj B., Yakovleva, Tatiana, Ronkina, Natalia, Suwandi, Abdulhadi, Odak, Ivan, Dhamija, Sonam, Sandrock, Inga, Hansmann, Florian, Baumgärtner, Wolfgang, Förster, Reinhold, Kotlyarov, Alexej, Gaestel, Matthias |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2296-634X, 795798 |
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