This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by James, J. Articles by Robbins, J. Search for Related Content PubMed PubMed Citation Articles by James, J. Articles by Robbins, J. Pubmed/NCBI databases Protein Substance via MeSH Related Collections Other myocardial biology

(Circulation. 2000;101:1715.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Genetic Manipulation of the Rabbit Heart via Transgenesis

Jeanne James, MD; Atsushi Sanbe, PhD; Karen Yager, PhD; Lisa Martin; Raisa Klevitsky, MD; Jeffrey Robbins, PhD

From the Children’s Hospital Research Foundation, Cincinnati, Ohio.

Correspondence to Jeffrey Robbins, PhD, Division of Molecular Cardiovascular Biology, 3333 Burnet Ave, Cincinnati, OH 45229-3039. E-mail jeff.robbins{at}chmcc.org

Background—Transgenesis using cardiac-specific expression has been valuable in exploring cardiac structure-function relationships. To date, cardiac-selective studies have been confined to the mouse. However, the utility of the mouse is limited in certain, possibly critical, aspects with respect to cardiovascular function.

Methods and Results—To establish the potential validity of transgenic methodology for remodeling a larger mammalian heart, we explored cardiac-selective expression in transgenic rabbits. The murine - and ß-cardiac myosin heavy chain gene promoters were used to express a reporter gene, and transgene expression was quantified in cardiac, skeletal, and smooth muscles as well as in nonmuscle tissues. Although neither promoter exactly mimics endogenous patterns of myosin heavy chain expression, both are able to drive high levels of transgene expression in the cardiac compartment. Neither promoter is active in smooth muscle or nonmuscle tissues.

Conclusions—Directed organ-specific expression is feasible in a larger animal with existing reagents, and cardiac-selective transgenic manipulation is possible in the rabbit.

Key Words: myosin • genes • muscles

This article has been cited by other articles:

				T. Suzuki, B. M. Palmer, J. James, Y. Wang, Z. Chen, P. VanBuren, D. W. Maughan, J. Robbins, and M. M. LeWinter Effects of Cardiac Myosin Isoform Variation on Myofilament Function and Crossbridge Kinetics in Transgenic Rabbits Circ Heart Fail, July 1, 2009; 2(4): 334 - 341. [Abstract] [Full Text] [PDF]

				A. Sanbe, J. James, V. Tuzcu, S. Nas, L. Martin, J. Gulick, H. Osinska, S. Sakthivel, R. Klevitsky, K. S. Ginsburg, et al. Transgenic Rabbit Model for Human Troponin I-Based Hypertrophic Cardiomyopathy Circulation, May 10, 2005; 111(18): 2330 - 2338. [Abstract] [Full Text] [PDF]

				J. James, L. Martin, M. Krenz, C. Quatman, F. Jones, R. Klevitsky, J. Gulick, and J. Robbins Forced Expression of {alpha}-Myosin Heavy Chain in the Rabbit Ventricle Results in Cardioprotection Under Cardiomyopathic Conditions Circulation, May 10, 2005; 111(18): 2339 - 2346. [Abstract] [Full Text] [PDF]

				M. Krenz and J. Robbins Impact of beta-myosin heavy chain expression on cardiac function during stress J. Am. Coll. Cardiol., December 21, 2004; 44(12): 2390 - 2397. [Abstract] [Full Text] [PDF]

				J. James, Y. Zhang, H. Osinska, A. Sanbe, R. Klevitsky, T. E. Hewett, and J. Robbins Transgenic Modeling of a Cardiac Troponin I Mutation Linked to Familial Hypertrophic Cardiomyopathy Circ. Res., October 27, 2000; 87(9): 805 - 811. [Abstract] [Full Text] [PDF]

				F. J. Davis, M. Gupta, S. M. Pogwizd, E. Bacha, V. Jeevanandam, and M. P. Gupta Increased expression of alternatively spliced dominant-negative isoform of SRF in human failing hearts Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1521 - H1533. [Abstract] [Full Text] [PDF]