Targeted disruption of the mouse protein phosphatase ppm1l gene leads to structural abnormalities in the brain.
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/Δmice 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.
Department of Biochemistry, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Rie
R
Kusano
Department of Biochemistry, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Kousuke
K
Fujita
Department of Biochemistry, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Yasuharu
Y
Shinoda
Department of Biochemistry, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Yuko
Y
Nagaura
Animal Resource Development Unit, RIKEN Center for Life Science Technologies, Kobe, Japan.|Genetic Engineering Team, RIKEN Center for Life Science Technologies, Kobe, Japan.
Hiroshi
H
Kiyonari
Genetic Engineering Team, RIKEN Center for Life Science Technologies, Kobe, Japan.
Takaya
T
Abe
Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara, Japan.
Toshio
T
Watanabe
Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Yasuhisa
Y
Matsui
Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Japan.
Masahiro
M
Fukaya
Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Japan.
Hiroyuki
H
Sakagami
Creative interdisciplinary Research Division, The Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan.
Tatsuya
T
Sato
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Jun-Ichi
JI
Funahashi
Department of Biological Chemistry, College of Bioscience and Biotechnology, Chubu University, Kasugai, Japan.
Motoko
M
Ohnishi
Department of Biochemistry, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Shinri
S
Tamura
Department of Biochemistry, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. takayasu.kobayashi.d7@tohoku.ac.jp.|Center for Gene Research, Tohoku University, Sendai, Japan. takayasu.kobayashi.d7@tohoku.ac.jp.
Takayasu
T
Kobayashi
D000818:Animals; D001921:Brain / Q000002:abnormalities* / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020935:MAP Kinase Signaling System; D051379:Mice; D010749:Phosphoprotein Phosphatases / Q000172:deficiency*
D010749:Phosphoprotein Phosphatases; C528435:Ppm1l protein, mouse
MAPK signaling; brain development; commissural tract; ppm1l; protein phosphatase; striatum