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Septin7 regulates inner ear formation at an early developmental stage / Septin7は内耳初期発生を制御するTorii, Hiroko 23 July 2018 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21295号 / 医博第4384号 / 新制||医||1030(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 影山 龍一郎, 教授 浅野 雅秀, 教授 辻川 明孝 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DAM
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Lyz2-Cre-Mediated Genetic Deletion of Septin7 Reveals a Role of Septins in Macrophage Cytokinesis and Kras-Driven TumorigenesisMenon, Manoj B., Yakovleva, Tatiana, Ronkina, Natalia, Suwandi, Abdulhadi, Odak, Ivan, Dhamija, Sonam, Sandrock, Inga, Hansmann, Florian, Baumgärtner, Wolfgang, Förster, Reinhold, Kotlyarov, Alexej, Gaestel, Matthias 03 April 2023 (has links)
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.
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