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

• Published in: FEBS letters Vol. 590; no. 20; pp. 3606 - 3615
• Main Authors: Kusano, Rie, Fujita, Kousuke, Shinoda, Yasuharu, Nagaura, Yuko, Kiyonari, Hiroshi, Abe, Takaya, Watanabe, Toshio, Matsui, Yasuhisa, Fukaya, Masahiro, Sakagami, Hiroyuki, Sato, Tatsuya, Funahashi, Jun‐ichi, Ohnishi, Motoko, Tamura, Shinri, Kobayashi, Takayasu
• Format: Journal Article
• Language: English
• Published: England 01.10.2016
• Subjects: Animals; Brain - abnormalities; Brain - growth & development; Brain - metabolism; brain development; commissural tract; Gene Expression Regulation, Developmental; MAP Kinase Signaling System; MAPK signaling; Mice; Phosphoprotein Phosphatases - deficiency; ppm1l; protein phosphatase; striatum; brain development; commissural tract; striatum; ppm1l; protein phosphatase; MAPK signaling
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1002/1873-3468.12429

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 ppm1lΔ/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.