Genetics
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Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Chapters
Summary August 8th, 2022
Based on the familial hereditary cardiomyopathy family found in our clinical work, we created a C57BL/6N mouse model with a point mutation (G823E) at the mouse MYH7 locus through CRISPR/Cas9-mediated genome engineering to verify this mutation.
Transcript
This protocol is significant as it can provide a demonstration of ultrasound in small animals. This technique may provide insights into the discovery of pathogenic genes in hereditary cardiomyopathy. Fix the knockin mice horizontally on the platform then tilt the platform 30 degrees coddle to the knockin mouse.
Remove hair on the anterior chest wall of the knockin mice using a depilatory cream position the probe vertically with the bump facing the animal's head. Then rotate the probe counterclockwise approximately 45 degrees in the para sternal long axis view. Rotate the probe 90 degrees clockwise to obtain the para sternal short axis view.
After rotating the probe, adjust the Y axis displacement to get the correct slice. Observe the long axis image of the heart and then select M mode measurement data. Acquire ultrasound data from para sternal long axis views of mice and measure the heart rate, left ventricular ejection fraction, cardiac output, left ventricular and diastolic dimension, left ventricular and systolic dimension.
Left ventricular posterior wall and ventricular septum. The family pedigrees of hypertrophic cardiomyopathy were obtained, and all the documented family members were diagnosed with hypertrophic cardiomyopathy enrollment. Sanger sequencing confirmed the same M Y H 7 P G 8 23 E variant in all patients, but not in the healthy individuals in the families.
And 174 controls, the heterozygous M Y H 7 P G 8 23 E completely co segregated in this family. The glycine residue at Codon 8 23 in the neck domain region of M Y H 7 was highly conserved in all the available vertebrate myocin sequences. According to A C M G standards and guidelines the M Y H 7 P G 8 23 E variant was predicted to be a pathogenic variant.
The knockin mice developed age-dependent cardiac hypertrophy after birth. Echocardiography revealed that the inter ventricular septum and left ventricular posterior wall developed with increased heart rate in the knockin mice. Also confirmed by the histological analysis.
Virus ultrasound data can be obtained by rotating the probe at different angles on different sections of the mouse term.
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