A-Band Titin Truncation in Zebrafish Causes Dilated Cardiomyopathy and Hemodynamic Stress Intolerance

Autor: Delfine Cheng, Wolfgang A. Linke, Inken G. Huttner, Gunjan Trivedi, Marion von Frieling-Salewsky, Christine E. Seidman, Jonathan G. Seidman, Daniel Hesselson, Timothy J. Bemand, Renee Johnson, Filip Braet, Karen Hillcoat, Kevin Alford, Diane Fatkin, Christopher S. Hayward, Claire Horvat, Louis W. Wang, Celine F. Santiago, Michael P. Feneley
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Embryo
Nonmammalian
Truncation
Adaptation
Biological
Hemodynamics
030204 cardiovascular system & hematology
Animals
Genetically Modified
0302 clinical medicine
Connectin
Zebrafish
Sequence Deletion
education.field_of_study
biology
Heart
Dilated cardiomyopathy
General Medicine
Middle Aged
musculoskeletal system
Pedigree
cardiovascular system
Cardiology
Female
Titin
Adult
Cardiomyopathy
Dilated
Heart Defects
Congenital
Sarcomeres
medicine.medical_specialty
Adolescent
Population
complex mixtures
Young Adult
03 medical and health sciences
Stress
Physiological
Internal medicine
medicine
Animals
Humans
In patient
cardiovascular diseases
education
Hemodynamic stress
Genetic Association Studies
Aged
business.industry
Stroke Volume
medicine.disease
biology.organism_classification
030104 developmental biology
biology.protein
business
Zdroj: Circulation: Genomic and Precision Medicine. 11
ISSN: 2574-8300
DOI: 10.1161/circgen.118.002135
Popis: Background Truncating variants in the TTN gene ( TTNtv) are common in patients with dilated cardiomyopathy (DCM) but also occur in the general population. Whether TTNtv are sufficient to cause DCM or require a second hit for DCM manifestation is an important clinical issue. Methods We generated a zebrafish model of an A-band TTNtv identified in 2 human DCM families in which early-onset disease appeared to be precipitated by ventricular volume overload. Cardiac phenotypes were serially assessed from 0 to 12 months using video microscopy, high-frequency echocardiography, and histopathologic analysis. The effects of sustained hemodynamic stress resulting from an anemia-induced hyperdynamic state were also evaluated. Results Homozygous ttna mutants had severe cardiac dysmorphogenesis and premature death, whereas heterozygous mutants ( ttna
Databáze: OpenAIRE
Externí odkaz: