Abstract 251: Development of a Transgenic Goat Model with Cardiac-Specific Overexpression of Transforming Growth Factor-β1 to Study the Relationship Between Atrial Fibrosis and Atrial Fibrillation
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Le résumé fourni par la source
Studies on patients, large animal models and transgenic mouse models have shown a strong association of atrial fibrosis with atrial fibrillation (AF). However, it is unclear whether there is a causal relationship between atrial fibrosis and AF or whether these events appear as a result of independent pathological changes in the heart. We are testing the hypothesis that goats that overexpress TGF-β1 (transforming growth factor beta1) specifically in cardiac myocytes will develop atrial fibrosis that in turn will lead to AF. Many aspects of AF-related remodeling have been studied comprehensively in goat models. However, these AF models are typically mechanically induced (eg, the rapid atrial pacing model). This unique transgenic goat model has the potential to offer insights into the role of fibrosis in AF initiation and progression without the confounding effects of mechanical AF induction. Somatic cell nuclear transfer (SCNT or cloning) was used to produce TGF-β1 transgenic pregnancies. First, pcDNA3.1DV5-MHC-TGF-β1cys33ser vector was constructed by subcloning the MHC-TGF-β1 fragment from the plasmid pUC-BM20-MHC-TGF-β1 into the pcDNA3.1D V5 vector. The NeonTM transfection system was used to electroporate primary goat fetal fibroblasts. After two weeks of G418 selection, the resulting G418 resistant colonies were screened by PCR to confirm transgene integration into goat genomic DNA. PCR positive cells were used for SCNT. Cloned embryos (n=264) were cultured for 12-60 h in vitro and then transferred into synchronized recipient females (n=15). Confirmation of pregnancy was done by ultrasonography on day 30 post-transfer. At the time of this abstract submission, 40% (6/15) of recipients were confirmed to be pregnant as determined by the presence of a heartbeat. The range for the stage of gestation is between day-60 and day-120. The first delivery date is April 28, 2012. Several reports documented no pregnancy losses after 30 days of gestation in goats. Therefore, we expect that most if not all of these pregnancies will result in delivery of live offspring. To our knowledge, this will be the first transgenic goat model generated for cardiovascular research.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Abstract 251: Development of a Transgenic Goat Model with Cardiac-Specific Overexpression of Transforming Growth Factor-β1 to Study the Relationship Between Atrial Fibrosis and Atrial Fibrillation
- Date Crossref
- 03/08/2012
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Utah State University pays non établi dans la noticeUniversité ou école supérieure
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Jiangsu Yonggang Group (China) pays non établi dans la noticeEntreprise
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Agricultural Research Service pays non établi dans la noticeOrganisme public
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University of Utah pays non établi dans la noticeUniversité ou école supérieure
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Irina A Polejaeva pays non établi dans la noticeInstitution
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Justin Hall pays non établi dans la noticeInstitution
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Qinggang Meng pays non établi dans la noticeInstitution
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Xinchang Zhou pays non établi dans la noticeInstitution
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Benjamin R Sessions pays non établi dans la noticeInstitution
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USDA ARS pays non établi dans la noticeInstitution
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Kip Panter pays non établi dans la noticeInstitution
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Rusty Stott pays non établi dans la noticeInstitution
Utah State University, Jiangsu Yonggang Group (China) et Agricultural Research Service, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.