Sean M. Rash

Normal cochlear function in mdx and mdxCv3 duchenne muscular dystrophy mouse models

Objectives/Hypothesis: Sensorineural hearing loss has been found in association with inherited muscular dystrophies in humans and in mouse models. An increased brainstem auditory evoked response threshold has been previously reported in the dystrophin‐deficient mdx mouse model for Duchenne muscular dystrophy, suggesting that full‐length dystrophin (Dp427) is involved in hearing. The objective of the present study was to confirm cochlear dysfunction with this gene defect and determine whether the shorter carboxyl terminus isoforms of dystrophin are also critical in maintaining normal hearing.

Congenital Muscular Dystrophy Mouse Model dy/dy Has Hypertrophic Cardiomyopathy by Echocardiography † 137

Congenital Muscular Dystrophy Mouse Model dy/dy Has Hypertrophic Cardiomyopathy by Echocardiography † 137

Muscular Dystrophy Mouse Models and Congenital Sensorineural Hearing Deficits: Implication of Muscle Proteins in Inner Ear Function

Muscular Dystrophy Mouse Models and Congenital Sensorineural Hearing Deficits: Implication of Muscle Proteins in Inner Ear Function

Ant1 -Deficient Mouse Model for Sengers Mitochondrial Myopathy Has Dilated Cardiomyopathy by Echocardiography

Ant1 -Deficient Mouse Model for Sengers Mitochondrial Myopathy Has Dilated Cardiomyopathy by Echocardiography

Echo- and Electrocardiography in Mice: Establishment of Methods for Assessing Cardiac Function in Mutant Strains. • 132

Clinical evaluation of cardiac function in man involves echocardiography and electrocardiography to assess morphology and electrical activity. Development of genetically altered mice provides transgenic and knockout strains which may display abnormalities in myocardial function or cardiac signal transduction. Routine techniques for clinical cardiac evaluation in mouse models have not been available. We have developed and applied echocardiography and electrocardiography in mice. We studied male C57BL/6J mice, a common background strain for developing mouse mutants. Mice were sedated with a mixture of ketamine, xylazine, and acepromazine. Echocardiography: The mice were studied at 8 to 10 weeks of age using a state-of-the-art Toshiba ultrasound system with rapid frame rate acquisition and a 7.5MHz transducer to produce high resolution M-mode sonographic images. This system permits accurate dynamic measurement of cardiac chamber size and wall thickness in mice. Using long axis M-mode images we measured: left ventricle inner diameter in systole and diastole (LVIDs and LVIDd), interventricular septum thickness in systole and diastole (IVSs and IVSd), and posterior left ventricular wall thickness in systole and diastole(LVPWs and LVPWd). RR interval was measured from simultaneous ECG tracing. Shortening fraction (SF), left ventricular ejection time corrected for heart rate (ETc), velocity of circumferential fiber shortening corrected for heart rate (VCFc) and left ventricular mass (LVM) were derived. Electrocardiography: The mice were studied at 12 to 14 weeks of age using a five lead system (three limb, one chest and one back), MacLab digitizing board and SCOPE software. RR, PR, QT and QTc intervals, QRS duration, and P, Q, R, S, and T wave voltages were measured. Scalar QRS axis was calculated. Average electro- and echocardiographic measurements were determined. In conclusion, cardiac abnormalities may exist in genetically altered mice necessitating the application of standard techniques for clinical assessment of cardiac function. We have successfully applied echocardiography and electrocardiography to the C57BL/6J mouse strain.