Abstract Details

Title Pathological and Behavioral Characterization of Transgenic Mice Expressing ALS-Associated CHCHD10-R15L

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S54 - Motor Neuron Disease (4:03 PM-4:14 PM)

Poster/Presentation
Number 004

Background Mutations in Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10 (CHCHD10) have been identified in patients suffering from various degenerative diseases including, but not limited to, ALS and mitochondrial myopathy. Transgenic mouse models have been valuable tools to study neurodegenerative diseases and we have sought to use this approach to investigate the mechanism(s) by which CHCHD10-R15L causes ALS.

Objective To develop a CHCHD10-R15L transgenic mouse model of amyotrophic lateral sclerosis (ALS) in order to investigate disease pathogenesis.

Design/Methods Transgenic mice expressing either CHCHD10-WT or CHCHD10-R15L under the control of the endogenous CHCHD10 promoter were developed. Pathological and behavioral characterization of these mouse lines at different timepoints was carried out.

Results Three CHCHD10-R15L transgenic lines were established. CHCHD10-R15L transgenic mice have an abbreviated lifespan compared to controls that is copy-number dependent. Central nervous system (CNS), skeletal muscle and cardiac pathology is apparent in CHCHD10-R15L transgenic mice. Severe axonal pathology is apparent in a diverse range of neurons throughout the CNS in CHCHD10-R15L transgenic mice. Despite the obvious pathology, CHCHD10-R15L transgenic mice perform comparably to control mice in motor behavioral tasks until very close to death.

Conclusions These novel mouse models support the hypothesis that CHCHD10-R15L impacts upon normal CNS functioning, as evident by the presence of axonal pathology. This, combined with the skeletal muscle and cardiac pathology results in early death that is not preceded by paralysis. These data suggest a combined role for CNS, skeletal muscle and/or cardiac dysfunction in CHCHD10-R15L disease pathogenesis.

Authors/Disclosures
Eanna Barra Ryan (Northwestern University) PRESENTER	No disclosure on file
Jianhua Yan, PhD (Northwestern University)	No disclosure on file
Han-Xiang Deng, MD	Dr. Deng has nothing to disclose.
Teepu Siddique, MD, FAAN	No disclosure on file

��ɫ��

��ɫ��