- AutorIn
- Manoj B. Menon
- Tatiana Yakovleva
- Natalia Ronkina
- Abdulhadi Suwandi
- Ivan Odak
- Sonam Dhamija
- Inga Sandrock
- Florian Hansmann
- Wolfgang Baumgärtner
- Reinhold Förster
- Alexej Kotlyarov
- Matthias Gaestel
- Titel
- Lyz2-Cre-Mediated Genetic Deletion of Septin7 Reveals a Role of Septins in Macrophage Cytokinesis and Kras-Driven Tumorigenesis
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:15-qucosa2-845154
- Quellenangabe
- Frontiers in cell and developmental biology
Erscheinungsjahr: 2021
Jahrgang: 9
E-ISSN: 2296-634X
Artikelnummer: 795798 - Erstveröffentlichung
- 2021
- Abstract (EN)
- 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.
- Andere Ausgabe
- Link zur Erstveröffentlichung
Link: https://doi.org/10.3389/fcell.2021.795798 - Freie Schlagwörter (EN)
- septins, septin7, Lyz2-Cre, phagocytosis, myeloid cells, tumor model, Kras-G12D
- Klassifikation (DDC)
- 570
- Verlag
- Frontiers Research Foundation, Lausanne
- Version / Begutachtungsstatus
- publizierte Version / Verlagsversion
- URN Qucosa
- urn:nbn:de:bsz:15-qucosa2-845154
- Veröffentlichungsdatum Qucosa
- 03.04.2023
- Dokumenttyp
- Artikel
- Sprache des Dokumentes
- Englisch
- Lizenz / Rechtehinweis
- CC BY 4.0