title: An animal model with a cardiomyocyte-specific deletion of estrogen receptor alpha: functional, metabolic, and differential network analysis.
abstract: 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 ERα allele (cs-ERα-/-). Male and female cs-ERα-/- 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-ERα-/- 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 ERα to characterize the role of ERα in the heart independent of systemic effects. Our results suggest that ERα is involved in controlling the expression of diverse genes and networks in the cardiomyocyte in a sex-dependent manner.
authors.affiliation: Department of Radiology, Washington University in St. Louis, Saint Louis, Missouri, United States of America.
authors.forename: Sriram
authors.initials: S
authors.lastname: Devanathan
authors.affiliation: Department of Radiology, Washington University in St. Louis, Saint Louis, Missouri, United States of America.
authors.forename: Timothy
authors.initials: T
authors.lastname: Whitehead
authors.affiliation: Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University in St. Louis, Saint Louis, Missouri, United States of America.
authors.forename: George G
authors.initials: GG
authors.lastname: Schweitzer
authors.affiliation: Department of Radiology, Washington University in St. Louis, Saint Louis, Missouri, United States of America.
authors.forename: Nicole
authors.initials: N
authors.lastname: Fettig
authors.affiliation: Center for Cardiovascular Research, Department of Medicine, Washington University in St. Louis, Saint Louis, Missouri, United States of America.
authors.forename: Attila
authors.initials: A
authors.lastname: Kovacs
authors.affiliation: Laboratory of Reproductive and Developmental Toxicology, Receptor Biology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Korach
authors.affiliation: Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University in St. Louis, Saint Louis, Missouri, United States of America.
authors.forename: Brian N
authors.initials: BN
authors.lastname: Finck
authors.affiliation: Department of Radiology, Washington University in St. Louis, Saint Louis, Missouri, United States of America; Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, Missouri, United States of America; Division of Biology and Biomedical Sciences, Washington University in St. Louis, Saint Louis, Missouri, United States of America.
authors.forename: Kooresh I
authors.initials: KI
authors.lastname: Shoghi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D047628:Estrogen Receptor alpha