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Menon, Manoj B. [Author]; Yakovleva, Tatiana [Author]; Ronkina, Natalia [Author]; Suwandi, Abdulhadi [Author]; Odak, Ivan [Author]; Dhamija, Sonam [Author]; Sandrock, Inga [Author]; Hansmann, Florian [Author]; Baumgärtner, Wolfgang [Author]; Förster, Reinhold [Author]; Kotlyarov, Alexej [Author]; Gaestel, Matthias [Author]

Lyz2-Cre-Mediated Genetic Deletion of Septin7 Reveals a Role of Septins in Macrophage Cytokinesis and Kras-Driven Tumorigenesis

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  • Media type: E-Article
  • Title: Lyz2-Cre-Mediated Genetic Deletion of Septin7 Reveals a Role of Septins in Macrophage Cytokinesis and Kras-Driven Tumorigenesis
  • Contributor: Menon, Manoj B. [Author]; Yakovleva, Tatiana [Author]; Ronkina, Natalia [Author]; Suwandi, Abdulhadi [Author]; Odak, Ivan [Author]; Dhamija, Sonam [Author]; Sandrock, Inga [Author]; Hansmann, Florian [Author]; Baumgärtner, Wolfgang [Author]; Förster, Reinhold [Author]; Kotlyarov, Alexej [Author]; Gaestel, Matthias [Author]
  • Published: Lausanne: Frontiers Research Foundation, [2023]
  • Published in: Frontiers in cell and developmental biology ; 9, (2021)
  • Language: English
  • Keywords: septins ; Lyz2-Cre ; phagocytosis ; septin7 ; tumor model ; Kras-G12D ; myeloid cells
  • Origination:
  • Footnote:
  • Description: By crossing septin7-floxed mice with Lyz2-Cre mice carrying the Cre recombinase insertedin the Lysozyme-M (Lyz2) gene locus we aimed the specific deletion of septin7 in myeloidcells, such as monocytes, macrophages and granulocytes. Septin7flox/flox:Lyz2-Cre miceshow no alterations in the myeloid compartment. Septin7-deleted macrophages (BMDMs)were isolated and analyzed. The lack of Septin7 expression was confirmed and aconstitutive double-nucleation was detected in Septin7-deficient BMDMs indicating adefect in macrophage cytokinesis. However, phagocytic function of macrophages asjudged by uptake of labelled E. coli particles and LPS-stimulated macrophage activation asjudged 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). Wemonitored lung adenocarcinoma formation in these mice by crossing them with theconditional knock-in Kras-LSL-G12D allele. Interestingly, we found that control micewithout septin7 depletion die after 3–5 weeks, while the Septin7-deficient animalssurvived 11 weeks or even longer. Control mice sacrificed in the age of 4 weeksdisplay a bronchiolo-alveolar hyperplasia with multiple adenomas, whereas theSeptin7-deficient animals of the same age are normal or show only a weak multifocalbrochiolo-alveolar hyperplasia. Our findings indicate an essential role of Septin7 inmacrophage cytokinesis but not in macrophage function. Furthermore, septin7 seemsabsolutely essential for oncogenic Kras-driven lung tumorigenesis making it a potentialtarget for anti-tumor interventions.
  • Access State: Open Access
  • Rights information: Attribution (CC BY)