Oct 11 2019

Vanishing white matter disease (VWM) is a familial neurological disease which chronically and progressively affect white matter in the brain. The VWM patients may show an episode of rapid neurological deterioration after exposure to various kind of stresses. A team at Niigata University, including Associate Professor Mika Terumitsu-Tsujita (presently at School of Medicine, Keio University), Professor Hironaka Igarashi, Associate Professor Hiroki Kitaura (Brain Research Institute), and Professor Hirohide Takebayashi (Graduate School of Medical and Dental Sciences) found mutant mice that exhibited a small body, movement disorder, and neurological symptoms such as epileptic seizures. They named the mutant mice “toy” and then identified a missense mutation in Eif2b5 gene as a cause for these phenotypes. The toy mutation in Eif2b5 gene result in reduced enzymatic activity of eIF2B, a translation initiation factor involved in protein synthesis. In humans, mutations in EIF2B5 gene are known to cause VWM. This study has shown that the toy mice could be a new mouse model of VWM. Investigation on pathogenesis of toy mice may pave the way for the development of a new treatment for VWM.

This study was conducted as a joint project by Niigata University, RIKEN, the University of Tokyo, and the National Center of Neurology and Psychiatry.

Publication Details

Title: Glial pathology in a novel spontaneous mutant mouse of the Eif2b5 gene: a vanishing white matter disease model

Journal: Journal of Neurochemistry

Authors: Mika Terumitsu-Tsujita, Hiroki Kitaura, Ikuo Miura, Yuji Kiyama, Fumiko Goto, Yoshiko Muraki, Shiho Ominato, Norikazu Hara, Anna Simankova, Norihisa Bizen, Kazuhiro Kashiwagi, Takuhiro Ito, Yasuko Toyoshima, Akiyoshi Kakita, Toshiya Manabe, Shigeharu Wakana, Hirohide Takebayashi, Hironaka Igarashi

DOI: 10.1111/jnc.14887