Open Access
ECG in neonate mice with spinal muscular atrophy allows assessment of drug efficacy
Christopher R. Heier1,2,3,Christine J. DiDonato2,3,*
Center for Genetic Medicine Research, Children’s National Medical Center, Washington, DC
Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL
Human Molecular Genetics Program, Ann & Robert H. Lurie Children’s Hospital of Chicago Research Center, Chicago, IL
DOI: 10.2741/E721 Volume 7 Issue 1, pp.122-133
Published: 01 January 2015
(This article belongs to the Special Issue Pre-mRNA splicing and human diseases)
*Corresponding Author(s):  
Christine J. DiDonato

Molecular technologies have produced diverse arrays of animal models for studying genetic diseases and potential therapeutics. Many have neonatal phenotypes. Spinal muscular atrophy (SMA) is a neuromuscular disorder primarily affecting children, and is of great interest in translational medicine. The most widely used SMA mouse models require all phenotyping to be performed in neonates since they do not survive much past weaning. Pre-clinical studies in neonate mice can be hindered by toxicity and a lack of quality phenotyping assays, since many assays are invalid in pups or require subjective scoring with poor inter-rater variability. We find, however, that passive electrocardiography (ECG) recording in conscious 11-day old SMA mice provides sensitive outcome measures, detecting large differences in heart rate, cardiac conduction, and autonomic control resulting from disease. We find significant drug benefits upon treatment with G418, an aminoglycoside targeting the underlying protein deficiency, even in the absence of overt effects on growth and survival. These findings provide several quantitative physiological biomarkers for SMA preclinical studies, and will be of utility to diverse disease models featuring neonatal cardiac arrhythmias.

Key words
ECG,Arrhythmia,Preclinical Outcome Measure,Phenotypic Assay,Mouse,Neonate,Spinal Muscular Atrophy,Translational Readthrough,SMN,Survival Motor Neuron,Review
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Christopher R. Heier, Christine J. DiDonato. ECG in neonate mice with spinal muscular atrophy allows assessment of drug efficacy. Frontiers in Bioscience-Elite. 2015. 7(1); 122-133.