Optimizing the Translational Value of Mouse Models of ALS for Dysphagia Therapeutic Discovery

Optimizing the Translational Value of Mouse Models of ALS for Dysphagia Therapeutic Discovery

The goal of this study was to compare dysphagia phenotypes in low and high copy number (LCN and HCN) transgenic superoxide dismutase 1 ( SOD1 ) mouse models of ALS to accelerate the discovery of novel and effective treatments for dysphagia and early amyotrophic lateral sclerosis (ALS) diagnosis. Cli...

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Bibliographic Details
Published in:Dysphagia Vol. 35; no. 2; pp. 343 - 359
Main Authors: Osman, Kate L., Kohlberg, Sabrina, Mok, Alexis, Brooks, Ryan, Lind, Lori A., McCormack, Katelyn, Ferreira, Andries, Kadosh, Matan, Fagan, Mary K., Bearce, Elizabeth, Nichols, Nicole L., Coates, Joan R., Lever, Teresa E.
Format: Journal Article
Language:English
Published: New York Springer US 01-04-2020
Springer
Springer Nature B.V
Subjects:
Age
Amyotrophic lateral sclerosis
Analysis
Animal models
Atrophy
Autopsy
Copy number
Deglutition disorders
Dysphagia
Gastroenterology
Genetic engineering
Hepatology
Imaging
Medicine
Medicine & Public Health
Original Article
Otorhinolaryngology
Paralysis
Pharynx
Phenotypes
Radiology
Rodents
Superoxide dismutase
Tongue
Transgenic mice
Translation
California
Deglutition
Videofluoroscopy
Dysphagia
Amyotrophic lateral sclerosis (ALS)
Deglutition disorders
Superoxide dismutase 1 (SOD1) transgenic mouse
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Summary:The goal of this study was to compare dysphagia phenotypes in low and high copy number (LCN and HCN) transgenic superoxide dismutase 1 ( SOD1 ) mouse models of ALS to accelerate the discovery of novel and effective treatments for dysphagia and early amyotrophic lateral sclerosis (ALS) diagnosis. Clinicopathological features of dysphagia were characterized in individual transgenic mice and age-matched controls utilizing videofluoroscopy in conjunction with postmortem assays of the tongue and hypoglossal nucleus. Quantitative PCR accurately differentiated HCN-SOD1 and LCN-SOD1 mice and nontransgenic controls. All HCN-SOD1 mice developed stereotypical paralysis in both hindlimbs. In contrast, LCN-SOD1 mice displayed wide variability in fore- and hindlimb involvement. Lick rate, swallow rate, inter-swallow interval, and pharyngeal transit time were significantly altered in both HCN-SOD1 and LCN-SOD1 mice compared to controls. Tongue weight, tongue dorsum surface area, total tongue length, and caudal tongue length were significantly reduced only in the LCN-SOD1 mice compared to age-matched controls. LCN-SOD1 mice with lower body weights had smaller/lighter weight tongues, and those with forelimb paralysis and slower lick rates died at a younger age. LCN-SOD1 mice had a 32% loss of hypoglossal neurons, which differed significantly when compared to age-matched control mice. These novel findings for LCN-SOD1 mice are congruent with reported dysphagia and associated tongue atrophy and hypoglossal nucleus pathology in human ALS patients, thus highlighting the translational potential of this mouse model in ALS research.
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ISSN:0179-051X
1432-0460
DOI:10.1007/s00455-019-10034-9