title: An animal model for late onset chronic demyelination disease caused by failed terminal differentiation of oligodendrocytes.
abstract: Various animal models are available for studying human multiple sclerosis (MS). Most of them model the initial phase of MS,including the immune-triggered attack of the myelin membrane and/or oligodendrocytes and, occasionally, demonstrate there mission and relapsing phases. However, few mimic the late chronic demyelinating phase. Overexpression of the proteolipid protein gene (Plp) causes a unique demyelinating disorder in mice in which normal-appearing myelin forms early in life and chronic demyelination occurs later. We found that remyelination is severely affected in this late demyelinating phase, but is not caused by deprivation of oligodendrocyte progenitors expressing PDGF receptor alpha (PDGFRa) and Olig2, which are present at an even higher number in the demyelinated white matter of the mutants than in wild-type controls. Furthermore, mature oligodendrocytes containing PLP were observed, but failed to remyelinate. The ability of oligodendrocytes from older transgenic animals to produce a myelin membrane-like structure was not impaired when cultured in vitro, which indicates that the lack of remyelination is not simply caused by changes in the intrinsic properties of the oligodendrocytes. Glial activation also occurred much earlier than active demyelination in mutant mice. Thus, in addition to intrinsic mechanisms, extrinsic mechanisms might also have an important role in defects of remyelination. These features are also observed in patients at a late stage of MS, leading to chronic demyelinating lesions. Thus, this mouse model partly mimics the late stage of MS and can be used to study the cause of inhibition of remyelination.
authors.affiliation: Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Japan.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Ma
authors.forename: Michio
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Kenji F
authors.initials: KF
authors.lastname: Tanaka
authors.forename: Hirohide
authors.initials: H
authors.lastname: Takebayashi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikenaka