An Animal Model with a Cardiomyocyte-Specific Deletion of Estrogen Receptor Alpha: Functional, Metabolic, and Differential Network Analysis

作者：Devanathan Sriram; Whitehead Timothy; Schweitzer George G; Fettig Nicole; Kovacs Attila; Korach Kenneth S; Finck Brian N; Shoghi Kooresh I^*

来源：PLos One, 2014, 9(7): e101900.

DOI：10.1371/journal.pone.0101900

Estrogen exerts diverse biological effects in multiple tissues in both animals and humans. Much of the accumulated knowledge on the role of estrogen receptor (ER) in the heart has been obtained from studies using ovariectomized mice, whole body ER gene knock-out animal models, ex vivo heart studies, or from isolated cardiac myocytes. In light of the wide systemic influence of ER signaling in regulating a host of biological functions in multiple tissues, it is difficult to infer the direct role of ER on the heart. Therefore, we developed a mouse model with a cardiomyocyte-specific deletion of the ER alpha allele (cs-ER alpha(-/-)). Male and female cs-ER alpha(-/-) mice with age/sex-matched wild type controls were examined for differences in cardiac structure and function by echocardiogram and differential gene expression microarray analysis. Our study revealed sex-differences in structural parameters in the hearts of cs-ER alpha(-/-) mice, with minimal functional differences. Analysis of microarray data revealed differential variations in the expression of 208 genes affecting multiple transcriptional networks. Furthermore, we report sex-specific differences in the expression of 56 genes. Overall, we developed a mouse model with cardiac-specific deletion of ER alpha to characterize the role of ER alpha in the heart independent of systemic effects. Our results suggest that ER alpha is involved in controlling the expression of diverse genes and networks in the cardiomyocyte in a sex-dependent manner.

• 出版日期2014-7-7
• 单位NIH