title: Severe Hypomyelination and Developmental Defects Are Caused in Mice Lacking Protein Arginine Methyltransferase 1 (PRMT1) in the Central Nervous System.
abstract: Protein arginine methyltransferase 1 (PRMT1) is involved in cell proliferation, DNA damage response, and transcriptional regulation. Although PRMT1 is extensively expressed in the CNS at embryonic and perinatal stages, the physiological role of PRMT1 has been poorly understood. Here, to investigate the primary function of PRMT1 in the CNS, we generated CNS-specific PRMT1 knock-out mice by the Cre-loxP system. These mice exhibited postnatal growth retardation with tremors, and most of them died within 2 weeks after birth. Brain histological analyses revealed prominent cell reduction in the white matter tracts of the mutant mice. Furthermore, ultrastructural analysis demonstrated that myelin sheath was almost completely ablated in the CNS of these animals. In agreement with hypomyelination, we also observed that most major myelin proteins including myelin basic protein (MBP), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), and myelin-associated glycoprotein (MAG) were dramatically decreased, although neuronal and astrocytic markers were preserved in the brain of CNS-specific PRMT1 knock-out mice. These animals had a reduced number of OLIG2(+) oligodendrocyte lineage cells in the white matter. We found that expressions of transcription factors essential for oligodendrocyte specification and further maturation were significantly suppressed in the brain of the mutant mice. Our findings provide evidence that PRMT1 is required for CNS development, especially for oligodendrocyte maturation processes.
authors.affiliation: From the Ph.D. Program in Human Biology, School of Integrative and Global Majors.
authors.forename: Misuzu
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Life Science Center, Tsukuba Advanced Research Alliance (TARA), and.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Murata
authors.affiliation: Life Science Center, Tsukuba Advanced Research Alliance (TARA), and Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577 and.
authors.forename: Junji
authors.initials: J
authors.lastname: Ishida
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577 and.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kanou
authors.affiliation: the Department of Biochemistry and Molecular Pharmacology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba 260-8670, Japan.
authors.forename: Yoshitoshi
authors.initials: Y
authors.lastname: Kasuya
authors.affiliation: From the Ph.D. Program in Human Biology, School of Integrative and Global Majors, Life Science Center, Tsukuba Advanced Research Alliance (TARA), and Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577 and akif@tara.tsukuba.ac.jp.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D019070:Cell Lineage; D049109:Cell Proliferation; D002490:Central Nervous System / Q000378:metabolism / Q000503:physiopathology*; D004249:DNA Damage; D017353:Gene Deletion; D005838:Genotype; D006023:Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011484:Protein-Arginine N-Methyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D004676:Myelin Basic Protein; C546338:Prmt1 protein, mouse; D011484:Protein-Arginine N-Methyltransferases
keywords: cell differentiation; central nervous system (CNS); myelin; oligodendrocyte; post-translational modification (PTM)