BMC cardiovascular disorders · 2025
Derivation of ultrasound and electrocardiogram cardiac reference ranges for Mus musculus using the collaborative cross and identification of new cardiac models.
СтатьяПоддержка правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Popp Julia L, Patel Krishna, Cuomo Danila, Lynch Rachel M, Leung Steve W, Berridge Brian R, Rusyn Ivan, Chiu Weihsueh A, Threadgill David W
Аннотация
BACKGROUND: Contemporary approaches for developing interventions and assessing pre-clinical cardiovascular risk frequently utilize animal and in vitro models. However, these models currently lack normal species-specific reference ranges similar to what exists for humans. The genetically diverse Collaborative Cross (CC) population that models human genetic heterogenetiety was characterized to develop mouse-specific cardiac reference ranges for Mus musculus, the most commonly used pre-clincial model.
METHODS: Heart function was analyzed in males and females from 58 CC strains and C57BL/6J using high-frequency ultrasound under both conscious and anesthetized conditions, as well as conscious electrocardiography to develop two standard deviation-based reference ranges. The sources and magnitude of measurement variability were identified, and inter-laboratory comparisons determined to quantify phenotypic robustness and heritability.
RESULTS: Strain was the largest source of variability, while laboratory where data were collected was also significant but sex was not. Additionally, strains were identified that have characteristics of disease-associated phenotypes in cardiac function and electrophysiology similar to human cases including dilated cardiomyopathy, cancer therapy-related cardiac dysfunction, and long QT.
CONCLUSIONS: These new models allow a more natural, and therefore more translatable progression to a cardiac disease state, supporting development of strain-specific models for cardiac pathologies, ultimately allowing more accurate diagnoses and informative human relevant assessments.
METHODS: Heart function was analyzed in males and females from 58 CC strains and C57BL/6J using high-frequency ultrasound under both conscious and anesthetized conditions, as well as conscious electrocardiography to develop two standard deviation-based reference ranges. The sources and magnitude of measurement variability were identified, and inter-laboratory comparisons determined to quantify phenotypic robustness and heritability.
RESULTS: Strain was the largest source of variability, while laboratory where data were collected was also significant but sex was not. Additionally, strains were identified that have characteristics of disease-associated phenotypes in cardiac function and electrophysiology similar to human cases including dilated cardiomyopathy, cancer therapy-related cardiac dysfunction, and long QT.
CONCLUSIONS: These new models allow a more natural, and therefore more translatable progression to a cardiac disease state, supporting development of strain-specific models for cardiac pathologies, ultimately allowing more accurate diagnoses and informative human relevant assessments.