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

10 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

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Age-dependent motor dysfunction due to neuron-specific disruption of stress-Activated protein kinase MKK7'. Together they form a unique fingerprint.

  • Cite this

    Yamasaki, T., Deki-Arima, N., Kaneko, A., Miyamura, N., Iwatsuki, M., Matsuoka, M., Fujimori-Tonou, N., Okamoto-Uchida, Y., Hirayama, J., Marth, J. D., Yamanashi, Y., Kawasaki, H., Yamanaka, K., Penninger, J. M., Shibata, S., & 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