Targeted disruption of the mouse protein phosphatase ppm1l gene leads to structural abnormalities in the brain

Rie Kusano; Kousuke Fujita; Yasuharu Shinoda; Yuko Nagaura; Hiroshi Kiyonari; Takaya Abe; Toshio Watanabe; Yasuhisa Matsui; Masahiro Fukaya; Hiroyuki Sakagami; Tatsuya Sato; Jun-Ichi Funahashi; Motoko Ohnishi; Shinri Tamura; Takayasu Kobayashi

doi:10.1002/1873-3468.12429

Targeted disruption of the mouse protein phosphatase ppm1l gene leads to structural abnormalities in the brain

FEBS Lett. 2016 Oct;590(20):3606-3615. doi: 10.1002/1873-3468.12429. Epub 2016 Sep 29.

Authors

Rie Kusano¹, Kousuke Fujita¹, Yasuharu Shinoda¹, Yuko Nagaura¹, Hiroshi Kiyonari^{2

3}, Takaya Abe³, Toshio Watanabe⁴, Yasuhisa Matsui⁵, Masahiro Fukaya⁶, Hiroyuki Sakagami⁶, Tatsuya Sato⁷, Jun-Ichi Funahashi⁸, Motoko Ohnishi⁹, Shinri Tamura¹, Takayasu Kobayashi^{10

11}

Affiliations

¹ Department of Biochemistry, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
² Animal Resource Development Unit, RIKEN Center for Life Science Technologies, Kobe, Japan.
³ Genetic Engineering Team, RIKEN Center for Life Science Technologies, Kobe, Japan.
⁴ Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara, Japan.
⁵ Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
⁶ Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Japan.
⁷ Creative interdisciplinary Research Division, The Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan.
⁸ Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
⁹ Department of Biological Chemistry, College of Bioscience and Biotechnology, Chubu University, Kasugai, Japan.
¹⁰ Department of Biochemistry, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. takayasu.kobayashi.d7@tohoku.ac.jp.
¹¹ Center for Gene Research, Tohoku University, Sendai, Japan. takayasu.kobayashi.d7@tohoku.ac.jp.

PMID: 27680501
DOI: 10.1002/1873-3468.12429

Abstract

PPM1L, a member of the metal-dependent protein phosphatase (PPM) family, is involved in regulating the stress-activated protein kinase pathway and ceramide trafficking. However, the physiological function of PPM1L in the brain is unclear. In this study, we generated and analyzed ppm1l-deficient mice in order to investigate PPM1L functions in the brain. Our results indicate that ppm1l is highly expressed in the central nervous system during mouse development and that ppm1l^Δ/Δ mice display impaired motor performance and morphological abnormalities in the forebrain. Electron microscopic and immunohistochemical analyses suggest that these abnormalities are due to impaired axonal tract formation. Our novel findings suggest an important role for PPM1L in brain development.

Keywords: MAPK signaling; brain development; commissural tract; ppm1l; protein phosphatase; striatum.

Publication types

Letter

MeSH terms

Animals
Brain / abnormalities*
Brain / growth & development
Brain / metabolism
Gene Expression Regulation, Developmental
MAP Kinase Signaling System
Mice
Phosphoprotein Phosphatases / deficiency*

Substances

Phosphoprotein Phosphatases
Ppm1l protein, mouse