Comparative Phenotypic Assessment of Cardiac Pathology, Physiology, and Gene Expression in C3H/HeJ, C57BL/6J, and B6C3F1/J Mice

Published on 2019-11-22T07:06:31Z (GMT) by
<div><p>Human cardiomyopathies often lead to heart failure, a major cause of morbidity and mortality in industrialized nations. Described here is a phenotypic characterization of cardiac function and genome-wide expression from C3H/HeJ, C57BL/6J, and B6C3F1/J male mice. Histopathologic analysis identified a low-grade background cardiomyopathy (murine progressive cardiomyopathy) in eight of nine male C3H/HeJ mice (age nine to ten weeks), but not in male C57BL/6J and in only of ten male B6C3F1/J mice. The C3H/HeJ mouse had an increased heart rate and a shorter RR interval compared to the B6C3F1/J and C57BL/6J mice. Cardiac genomic studies indicated the B6C3F1/J mice exhibited an intermediate gene expression phenotype relative to the 2 parental strains. Disease-centric enrichment analysis indicated a number of cardiomyopathy-associated genes were induced in B6C3F1/J and C3H/HeJ mice, including <i>Myh7, My14,</i> and <i>Lmna</i> and also indicated differential expression of genes associated with metabolic (e.g., <i>Pdk2</i>) and hypoxic stress (e.g. <i>Hif1a</i>). A novel coexpression and integrated pathway network analysis indicated <i>Prkaa2, Pdk2, Rhoj,</i> and <i>Sgcb</i> are likely to play a central role in the pathophysiology of murine progressive cardiomyopathy in C3H/HeJ mice. Our studies indicate that genetically determined baseline differences in cardiac phenotype have the potential to influence the results of cardiotoxicity studies.</p></div>

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Auerbach, Scott S.; Thomas, Reuben; Shah, Ruchir; Xu, Hong; Vallant, Molly K.; Nyska, Abraham; et al. (2010): Comparative Phenotypic Assessment of Cardiac Pathology, Physiology, and Gene Expression in C3H/HeJ, C57BL/6J, and B6C3F1/J Mice. SAGE Journals. Collection. https://doi.org/10.25384/SAGE.c.4750337.v1