Age-dependent motor dysfunction due to neuron-specific disruption of stress-Activated protein kinase MKK7

Tokiwa Yamasaki, Norie Deki-Arima, Asahito Kaneko, Norio Miyamura, Mamiko Iwatsuki, Masato Matsuoka, Noriko Fujimori-Tonou, Yoshimi Okamoto-Uchida, Jun Hirayama, Jamey D. Marth, Yuji Yamanashi, Hiroshi Kawasaki, Koji Yamanaka, Josef M. Penninger, Shigenobu Shibata, Hiroshi Nishina

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    c-Jun N-Terminal kinase (JNK) is a member of the mitogen-Activated protein kinase family and controls various physiological processes including apoptosis. A specific upstream activator of JNKs is the mitogen-Activated protein kinase kinase 7 (MKK7). It has been reported that MKK7-JNK signaling plays an important regulatory role in neural development, however, post-developmental functions in the nervous system have not been elucidated. In this study, we generated neuron-specific Mkk7 knockout mice (MKK7 cKO), which impaired constitutive activation of JNK in the nervous system. MKK7 cKO mice displayed impaired circadian behavioral rhythms and decreased locomotor activity. MKK7 cKO mice at 8 months showed motor dysfunctions such as weakness of hind-limb and gait abnormality in an age-dependent manner. Axonal degeneration in the spinal cord and muscle atrophy were also observed, along with accumulation of the axonal transport proteins JNK-interacting protein 1 and amyloid beta precursor protein in the brains and spinal cords of MKK7 cKO mice. Thus, the MKK7-JNK signaling pathway plays important roles in regulating circadian rhythms and neuronal maintenance in the adult nervous system.

    Original languageEnglish
    Article number7348
    JournalScientific Reports
    Volume7
    Issue number1
    DOIs
    Publication statusPublished - 2017 Dec 1

    Fingerprint

    MAP Kinase Kinase 7
    JNK Mitogen-Activated Protein Kinases
    Heat-Shock Proteins
    Protein Kinases
    Neurons
    Nervous System
    Circadian Rhythm
    Spinal Cord
    Physiological Phenomena
    Axonal Transport
    Muscular Atrophy
    Amyloid beta-Protein Precursor
    Locomotion
    Mitogen-Activated Protein Kinases
    Gait
    Knockout Mice
    MAP kinase kinase kinase 7
    Carrier Proteins
    Extremities
    Maintenance

    ASJC Scopus subject areas

    • General

    Cite this

    Yamasaki, T., Deki-Arima, N., Kaneko, A., Miyamura, N., Iwatsuki, M., Matsuoka, M., ... Nishina, H. (2017). Age-dependent motor dysfunction due to neuron-specific disruption of stress-Activated protein kinase MKK7. Scientific Reports, 7(1), [7348]. https://doi.org/10.1038/s41598-017-07845-x

    Age-dependent motor dysfunction due to neuron-specific disruption of stress-Activated protein kinase MKK7. / Yamasaki, Tokiwa; Deki-Arima, Norie; Kaneko, Asahito; Miyamura, Norio; Iwatsuki, Mamiko; Matsuoka, Masato; Fujimori-Tonou, Noriko; Okamoto-Uchida, Yoshimi; Hirayama, Jun; Marth, Jamey D.; Yamanashi, Yuji; Kawasaki, Hiroshi; Yamanaka, Koji; Penninger, Josef M.; Shibata, Shigenobu; Nishina, Hiroshi.

    In: Scientific Reports, Vol. 7, No. 1, 7348, 01.12.2017.

    Research output: Contribution to journalArticle

    Yamasaki, T, Deki-Arima, N, Kaneko, A, Miyamura, N, Iwatsuki, M, Matsuoka, M, Fujimori-Tonou, N, Okamoto-Uchida, Y, Hirayama, J, Marth, JD, Yamanashi, Y, Kawasaki, H, Yamanaka, K, Penninger, JM, Shibata, S & Nishina, H 2017, 'Age-dependent motor dysfunction due to neuron-specific disruption of stress-Activated protein kinase MKK7', Scientific Reports, vol. 7, no. 1, 7348. https://doi.org/10.1038/s41598-017-07845-x
    Yamasaki, Tokiwa ; Deki-Arima, Norie ; Kaneko, Asahito ; Miyamura, Norio ; Iwatsuki, Mamiko ; Matsuoka, Masato ; Fujimori-Tonou, Noriko ; Okamoto-Uchida, Yoshimi ; Hirayama, Jun ; Marth, Jamey D. ; Yamanashi, Yuji ; Kawasaki, Hiroshi ; Yamanaka, Koji ; Penninger, Josef M. ; Shibata, Shigenobu ; Nishina, Hiroshi. / Age-dependent motor dysfunction due to neuron-specific disruption of stress-Activated protein kinase MKK7. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
    @article{3c4eaa14999c452aaaf9c88220bbc48a,
    title = "Age-dependent motor dysfunction due to neuron-specific disruption of stress-Activated protein kinase MKK7",
    abstract = "c-Jun N-Terminal kinase (JNK) is a member of the mitogen-Activated protein kinase family and controls various physiological processes including apoptosis. A specific upstream activator of JNKs is the mitogen-Activated protein kinase kinase 7 (MKK7). It has been reported that MKK7-JNK signaling plays an important regulatory role in neural development, however, post-developmental functions in the nervous system have not been elucidated. In this study, we generated neuron-specific Mkk7 knockout mice (MKK7 cKO), which impaired constitutive activation of JNK in the nervous system. MKK7 cKO mice displayed impaired circadian behavioral rhythms and decreased locomotor activity. MKK7 cKO mice at 8 months showed motor dysfunctions such as weakness of hind-limb and gait abnormality in an age-dependent manner. Axonal degeneration in the spinal cord and muscle atrophy were also observed, along with accumulation of the axonal transport proteins JNK-interacting protein 1 and amyloid beta precursor protein in the brains and spinal cords of MKK7 cKO mice. Thus, the MKK7-JNK signaling pathway plays important roles in regulating circadian rhythms and neuronal maintenance in the adult nervous system.",
    author = "Tokiwa Yamasaki and Norie Deki-Arima and Asahito Kaneko and Norio Miyamura and Mamiko Iwatsuki and Masato Matsuoka and Noriko Fujimori-Tonou and Yoshimi Okamoto-Uchida and Jun Hirayama and Marth, {Jamey D.} and Yuji Yamanashi and Hiroshi Kawasaki and Koji Yamanaka and Penninger, {Josef M.} and Shigenobu Shibata and Hiroshi Nishina",
    year = "2017",
    month = "12",
    day = "1",
    doi = "10.1038/s41598-017-07845-x",
    language = "English",
    volume = "7",
    journal = "Scientific Reports",
    issn = "2045-2322",
    publisher = "Nature Publishing Group",
    number = "1",

    }

    TY - JOUR

    T1 - Age-dependent motor dysfunction due to neuron-specific disruption of stress-Activated protein kinase MKK7

    AU - Yamasaki, Tokiwa

    AU - Deki-Arima, Norie

    AU - Kaneko, Asahito

    AU - Miyamura, Norio

    AU - Iwatsuki, Mamiko

    AU - Matsuoka, Masato

    AU - Fujimori-Tonou, Noriko

    AU - Okamoto-Uchida, Yoshimi

    AU - Hirayama, Jun

    AU - Marth, Jamey D.

    AU - Yamanashi, Yuji

    AU - Kawasaki, Hiroshi

    AU - Yamanaka, Koji

    AU - Penninger, Josef M.

    AU - Shibata, Shigenobu

    AU - Nishina, Hiroshi

    PY - 2017/12/1

    Y1 - 2017/12/1

    N2 - c-Jun N-Terminal kinase (JNK) is a member of the mitogen-Activated protein kinase family and controls various physiological processes including apoptosis. A specific upstream activator of JNKs is the mitogen-Activated protein kinase kinase 7 (MKK7). It has been reported that MKK7-JNK signaling plays an important regulatory role in neural development, however, post-developmental functions in the nervous system have not been elucidated. In this study, we generated neuron-specific Mkk7 knockout mice (MKK7 cKO), which impaired constitutive activation of JNK in the nervous system. MKK7 cKO mice displayed impaired circadian behavioral rhythms and decreased locomotor activity. MKK7 cKO mice at 8 months showed motor dysfunctions such as weakness of hind-limb and gait abnormality in an age-dependent manner. Axonal degeneration in the spinal cord and muscle atrophy were also observed, along with accumulation of the axonal transport proteins JNK-interacting protein 1 and amyloid beta precursor protein in the brains and spinal cords of MKK7 cKO mice. Thus, the MKK7-JNK signaling pathway plays important roles in regulating circadian rhythms and neuronal maintenance in the adult nervous system.

    AB - c-Jun N-Terminal kinase (JNK) is a member of the mitogen-Activated protein kinase family and controls various physiological processes including apoptosis. A specific upstream activator of JNKs is the mitogen-Activated protein kinase kinase 7 (MKK7). It has been reported that MKK7-JNK signaling plays an important regulatory role in neural development, however, post-developmental functions in the nervous system have not been elucidated. In this study, we generated neuron-specific Mkk7 knockout mice (MKK7 cKO), which impaired constitutive activation of JNK in the nervous system. MKK7 cKO mice displayed impaired circadian behavioral rhythms and decreased locomotor activity. MKK7 cKO mice at 8 months showed motor dysfunctions such as weakness of hind-limb and gait abnormality in an age-dependent manner. Axonal degeneration in the spinal cord and muscle atrophy were also observed, along with accumulation of the axonal transport proteins JNK-interacting protein 1 and amyloid beta precursor protein in the brains and spinal cords of MKK7 cKO mice. Thus, the MKK7-JNK signaling pathway plays important roles in regulating circadian rhythms and neuronal maintenance in the adult nervous system.

    UR - http://www.scopus.com/inward/record.url?scp=85026821210&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=85026821210&partnerID=8YFLogxK

    U2 - 10.1038/s41598-017-07845-x

    DO - 10.1038/s41598-017-07845-x

    M3 - Article

    C2 - 28779160

    AN - SCOPUS:85026821210

    VL - 7

    JO - Scientific Reports

    JF - Scientific Reports

    SN - 2045-2322

    IS - 1

    M1 - 7348

    ER -