RRC ID |
82620
|
Author |
Miyamoto Y, Tanaka M, Ito H, Ooizumi H, Ohbuchi K, Mizoguchi K, Torii T, Yamauchi J.
|
Title |
Expression of kinase-deficient MEK2 ameliorates Pelizaeus-Merzbacher disease phenotypes in mice.
|
Journal |
Biochem Biophys Res Commun
|
Abstract |
Pelizaeus-Merzbacher disease (PMD) is characterized as a congenital hypomyelinating disorder in oligodendrocytes, myelin-forming glial cells in the central nervous system (CNS). The responsible gene of PMD is plp1, whose multiplication, deletion, or mutation is associated with PMD. We previously reported that primary oligodendrocytes overexpressing proteolipid protein 1 (PLP1) do not have the ability to differentiate morphologically, whereas inhibition of mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) by its cognate siRNA or chemical inhibitor reverses their undifferentiated phenotypes. Here, we show that oligodendrocyte-specific expression of kinase-deficient dominant-inhibitory mutant (MEK2K101A) of MAPK/ERK kinase 2 (MEK2), as the direct upstream molecule of MAPK/ERK in PMD model mice, promotes myelination in CNS tissues. Expression of MEK2K101A in PMD model mice also improves Rotor-rod test performance, which is often used to assess motor coordination in a rodent model with neuropathy. These results suggest that in PMD model mice, MEK2K101A can ameliorate impairments of myelination and motor function and that the signaling through MAPK/ERK may involve potential therapeutic target molecules of PMD in vivo.
|
Volume |
531(4)
|
Pages |
445-451
|
Published |
2020-10-22
|
DOI |
10.1016/j.bbrc.2020.07.131
|
PII |
S0006-291X(20)31532-1
|
PMID |
32800341
|
MeSH |
Animals
Brain / pathology
Disease Models, Animal
Female
Gene Expression Regulation, Enzymologic
Genes, Dominant
MAP Kinase Kinase 2 / genetics*
MAP Kinase Kinase 2 / metabolism
MAP Kinase Signaling System / genetics
Male
Mice, Transgenic
Mutation
Myelin Proteolipid Protein / genetics
Myelin Sheath / metabolism
Myelin Sheath / pathology
Pelizaeus-Merzbacher Disease / etiology*
Phenotype
Rotarod Performance Test
|
Resource |
Mice |
RBRC00999 |