PKN1 kinase-negative knock-in mice develop splenomegaly and leukopenia at advanced age without obvious autoimmune-like phenotypes.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
27 Sep 2019
Historique:
received: 25 03 2019
accepted: 30 08 2019
entrez: 29 9 2019
pubmed: 29 9 2019
medline: 3 11 2020
Statut: epublish

Résumé

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

Identifiants

pubmed: 31562379
doi: 10.1038/s41598-019-50419-2
pii: 10.1038/s41598-019-50419-2
pmc: PMC6764976
doi:

Substances chimiques

protein kinase N EC 2.7.1.-
Protein Kinase C EC 2.7.11.13

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

13977

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Auteurs

Salman Mahmud Siddique (SM)

Graduate School of Medicine, Kobe University, Kobe, 650-0017, Japan.

Koji Kubouchi (K)

Graduate School of Medicine, Kobe University, Kobe, 650-0017, Japan.

Yuka Shinmichi (Y)

Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kindai University, 3-4-1, Kowakae, Higashi-Osaka, 577- 8502, Japan.

Nana Sawada (N)

Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kindai University, 3-4-1, Kowakae, Higashi-Osaka, 577- 8502, Japan.

Reiko Sugiura (R)

Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kindai University, 3-4-1, Kowakae, Higashi-Osaka, 577- 8502, Japan.

Yasushi Itoh (Y)

Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan.

Shunsuke Uehara (S)

Department of Biochemistry, Matsumoto Dental University, Shiojiri, Nagano, 399-0781, Japan.

Kanae Nishimura (K)

Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma, Kobe, Hyogo, 654-0142, Japan.

Shunsuke Okamura (S)

Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma, Kobe, Hyogo, 654-0142, Japan.

Hiroyuki Ohsaki (H)

Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma, Kobe, Hyogo, 654-0142, Japan.

Shingo Kamoshida (S)

Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma, Kobe, Hyogo, 654-0142, Japan.

Yusuke Yamashita (Y)

Department of Hematology/Oncology, Wakayama Medical University, Wakayama, Japan.

Shinobu Tamura (S)

Department of Hematology/Oncology, Wakayama Medical University, Wakayama, Japan.

Takashi Sonoki (T)

Department of Hematology/Oncology, Wakayama Medical University, Wakayama, Japan.

Hiroshi Matsuoka (H)

Division of Medical Oncology and Hematology, Kobe University Hospital, Kobe, Hyogo, Japan.

Tomoo Itoh (T)

Department of Diagnostic Pathology, Kobe University Hospital, Kobe, Hyogo, 650-0017, Japan.

Hideyuki Mukai (H)

Graduate School of Medicine, Kobe University, Kobe, 650-0017, Japan. mukinase@kobe-u.ac.jp.
Biosignal Research Center, Kobe University, Kobe, 657- 8501, Japan. mukinase@kobe-u.ac.jp.

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