A Novel Adenoviral Vector-mediated Mouse Model of Charcot-Marie-Tooth Type 2D (CMT2D)

Overview

Journal J Mol Histol

Specialty Biochemistry

Date 2013 Aug 31

PMID 23990368

Citations 8

Authors

Ah Jung Seo

Youn Ho Shin

Seo Jin Lee

Doyeun Kim

Byung Sun Park

Sunghoon Kim

Kyu Ha Choi

Na Young Jeong

Chan Park

Ji-Yeon Jang

Youngbuhm Huh

Junyang Jung

Affiliations

Soon will be listed here.

Abstract

Charcot-Marie-Tooth disease type 2D is a hereditary axonal and glycyl-tRNA synthetase (GARS)-associated neuropathy that is caused by a mutation in GARS. Here, we report a novel GARS-associated mouse neuropathy model using an adenoviral vector system that contains a neuronal-specific promoter. In this model, we found that wild-type GARS is distributed to peripheral axons, dorsal root ganglion (DRG) cell bodies, central axon terminals, and motor neuron cell bodies. In contrast, GARS containing a G240R mutation was localized in DRG and motor neuron cell bodies, but not axonal regions, in vivo. Thus, our data suggest that the disease-causing G240R mutation may result in a distribution defect of GARS in peripheral nerves in vivo. Furthermore, a distributional defect may be associated with axonal degradation in GARS-associated neuropathies.

Citing Articles

Dominant aminoacyl-tRNA synthetase disorders: lessons learned from disease models.

Kalotay E, Klugmann M, Housley G, Frohlich D Front Neurosci. 2023; 17:1182845.

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An Integrated Approach to Studying Rare Neuromuscular Diseases Using Animal and Human Cell-Based Models.

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Anatomical distributional defects in mutant genes associated with dominant intermediate Charcot-Marie-Tooth disease type C in an adenovirus-mediated mouse model.

Lee S, Panthi S, Jo H, Cho J, Kim M, Jeong N Neural Regen Res. 2017; 12(3):486-492.

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Peripheral neuropathy via mutant tRNA synthetases: Inhibition of protein translation provides a possible explanation.

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