Title:
Genetic neuropathological analysis using gene trap mutant mice with dystonia phenotype

 

Hirohide Takebayashi
Division of Neurobiology and Anatomy,
Graduate School of Medical and Dental Sciences,
Niigata University

 

Abstract:
Dystonia is a movement disorder, which show involuntary movement. Dystonia muscurolum is a mutant mouse line, which shows dystonic phenotype with sensory neuron degeneration. The causative gene, Dystonin (Dst) encodes a cytoskeleton regulator protein, which bind tubulin and actin. In order to investigate the neuronal circuit, which is responsible for the movement phenotype of Dystonia musculorum mice, we generated a novel Dst gene trap (Dst^Gt) allele, which is multipurpose one for conditional knockout (cKO) and conditional rescue (cRescue) experiments. In the Dst^Gt homozygous mice, we observed sensory neuron degeneration and progressive dystonia phenotype during postnatal stages. Dystonia phenotype is also confirmed by electromyography. By histological analyses, we also observed neurofilament aggregation in the peripheral nervous system (PNS) and central nervous system (CNS) of the Dst^Gt homozygous mice. We are now performing conditional experiments (cKO and cRescue) utilizing Cre recombination and the Dst^Gt mice. I will discuss the usefulness of multipurpose genetrap mice, to identify neuronal circuit responsible for movement disorder and to understand pathogenesis of neurodegenerative disease.

 

References:
1. Horie M, Watanabe K, Bepari AK, Nashimoto J, Araki K, Sano H, Chiken S, Nambu A, Ono K, Ikenaka K, Kakita A, Yamamura K, Takebayashi H. Disruption of actin-binding domain-containing Dystonin protein causes dystonia musculorum in mice. Eur J Neurosci. 2014; 40: 3458-3471.

2. 竹林浩秀, 堀江正男. ジストニア症状を示す遺伝性神経難病モデルマウスの作製と解析 新潟医学会雑誌 129巻9号 2015.