PKN1 kinase-negative knock-in mice develop splenomegaly and leukopenia at advanced age without obvious autoimmune-like phenotypes
Protein kinase N1 (PKN1) knockout (KO) mice spontaneously form germinal centers (GCs) and develop an autoimmune-like disease with age. Here, we investigated the function of PKN1 kinase activity in vivo using aged mice deficient in kinase activity resulting from the introduction of a point mutation (T778A) in the activation loop of the enzyme. PKN1[T778A] mice reached adulthood without external abnormalities; however, the average spleen size and weight of aged PKN1[T778A] mice increased significantly compared to aged wild type (WT) mice. Histologic examination and Southern blot analyses of spleens showed extramedullary hematopoiesis and/or lymphomagenesis in some cases, although without significantly different incidences between PKN1[T778A] and WT mice. Additionally, flow cytometry revealed increased numbers in B220+, CD3+, Gr1+ and CD193+ leukocytes in the spleen of aged PKN1[T778A] mice, whereas the number of lymphocytes, neutrophils, eosinophils, and monocytes was reduced in the peripheral blood, suggesting an advanced impairment of leukocyte trafficking with age. Moreover, aged PKN1[T778A] mice showed no obvious GC formation nor autoimmune-like phenotypes, such as glomerulonephritis or increased anti-dsDNA antibody titer, in peripheral blood. Our results showing phenotypic differences between aged Pkn1-KO and PKN1[T778A] mice may provide insight into the importance of PKN1-specific kinase-independent functions in vivo.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Scientific reports - 9(2019), 1 vom: 27. Sept., Seite 13977 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Siddique, Salman Mahmud [VerfasserIn] |
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| Links: |
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| Themen: |
EC 2.7.1.- |
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| Anmerkungen: |
Date Completed 02.11.2020 Date Revised 10.01.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41598-019-50419-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM301700303 |
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| 100 | 1 | |a Siddique, Salman Mahmud |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a PKN1 kinase-negative knock-in mice develop splenomegaly and leukopenia at advanced age without obvious autoimmune-like phenotypes |
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| 520 | |a Protein kinase N1 (PKN1) knockout (KO) mice spontaneously form germinal centers (GCs) and develop an autoimmune-like disease with age. Here, we investigated the function of PKN1 kinase activity in vivo using aged mice deficient in kinase activity resulting from the introduction of a point mutation (T778A) in the activation loop of the enzyme. PKN1[T778A] mice reached adulthood without external abnormalities; however, the average spleen size and weight of aged PKN1[T778A] mice increased significantly compared to aged wild type (WT) mice. Histologic examination and Southern blot analyses of spleens showed extramedullary hematopoiesis and/or lymphomagenesis in some cases, although without significantly different incidences between PKN1[T778A] and WT mice. Additionally, flow cytometry revealed increased numbers in B220+, CD3+, Gr1+ and CD193+ leukocytes in the spleen of aged PKN1[T778A] mice, whereas the number of lymphocytes, neutrophils, eosinophils, and monocytes was reduced in the peripheral blood, suggesting an advanced impairment of leukocyte trafficking with age. Moreover, aged PKN1[T778A] mice showed no obvious GC formation nor autoimmune-like phenotypes, such as glomerulonephritis or increased anti-dsDNA antibody titer, in peripheral blood. Our results showing phenotypic differences between aged Pkn1-KO and PKN1[T778A] mice may provide insight into the importance of PKN1-specific kinase-independent functions in vivo | ||
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| 700 | 1 | |a Kubouchi, Koji |e verfasserin |4 aut | |
| 700 | 1 | |a Shinmichi, Yuka |e verfasserin |4 aut | |
| 700 | 1 | |a Sawada, Nana |e verfasserin |4 aut | |
| 700 | 1 | |a Sugiura, Reiko |e verfasserin |4 aut | |
| 700 | 1 | |a Itoh, Yasushi |e verfasserin |4 aut | |
| 700 | 1 | |a Uehara, Shunsuke |e verfasserin |4 aut | |
| 700 | 1 | |a Nishimura, Kanae |e verfasserin |4 aut | |
| 700 | 1 | |a Okamura, Shunsuke |e verfasserin |4 aut | |
| 700 | 1 | |a Ohsaki, Hiroyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Kamoshida, Shingo |e verfasserin |4 aut | |
| 700 | 1 | |a Yamashita, Yusuke |e verfasserin |4 aut | |
| 700 | 1 | |a Tamura, Shinobu |e verfasserin |4 aut | |
| 700 | 1 | |a Sonoki, Takashi |e verfasserin |4 aut | |
| 700 | 1 | |a Matsuoka, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Itoh, Tomoo |e verfasserin |4 aut | |
| 700 | 1 | |a Mukai, Hideyuki |e verfasserin |4 aut | |
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