Cardiac-Specific Manipulation in Transgenic Rabbits
Background
- A variety of human cardiac abnormalities or cardiac dysfunction can lead to heart failure, and a compromise in regional blood flow and tissue oxygenation.
- The study of such diseases and conditions in genetically diverse humans is difficult and unpredictable.
- The development of transgenic animal technology and the ability to manipulate gene expression has provided significant advances for obtaining more complete information about complex systems in vivo.
- While successful transgenic models have been created in a number of large and small animal species, the mouse has been the animal of choice for cardiovascular studies.
- However, there are significant differences between mouse models and human cardiac disease, particularly with regard to familial hypertrophic cardiomyopathies (FHC). Mouse models of FHC exhibit depressed contractility, absence of cardiac sudden death, a relatively small increase in ventricular mass, and a gender bias not found in human FHC.
- The mouse heart beats ten times faster than the human heart and the two species continue to diverge at the molecular level. The _-myosin heavy chain isoform predominates in the adult mouse ventricle while the _-myosin heavy chain isoform predominates in the adult human ventricles.
- Thus, development of a transgenic, cardiac-preferred expression model in a system closely related to the human heart at the molecular, biochemical, and physiologic levels is desirable, particularly for use in studying FHC.
Description of Current Technology
The current invention, created in the laboratory of Dr. Jeffrey Robbins, consists of an expression cassette comprising a promoter capable of initiating cardiac-preferred transcription operably linked to a heterologous nucleotide sequence. Such cassette contains a promoter capable of initiating ventricle-preferred or atria-preferred transcription in the rabbit, a model in which cardiac physiology and molecular biology is closely related to humans. In transgenic rabbits, expression of the heterologous nucleotide sequence is altered, particularly in cardiac tissue, and is linked to a promoter capable of initiating ventricle-preferred transcription exhibiting altered myosinisoform expression. The rabbit's susceptibility (including decreased susceptibility) to various cardiopathies, including cardiomyopathies such as FHC and dilated cardiomyopathies, may be altered by the methods of the invention. Expression of the heterologous nucleotide sequence can be assessed by using known methods and include _-myosin heavy chain, _-myosin heavy chain, essential myosin light chain-1, actin, catecholamine receptors, and glycogen synthase 3-_. Finally, methods for identifying anti-cardiopathic compounds are provided. This model system represents a valuable tool for broadening our understanding of the mechanisms of and developing new treatments for cardiomyopathies.
Objective
The Cincinnati Children's Research Foundation is seeking a biomedical corporate partner to sponsor research validating the utility of this invention and/or to utilize this model for commercial development of novel therapeutic agents in this field.
Contact
Parties interested in receiving further confidential information relative to this technology, kindly contact:
Joseph D. Fondacaro, PhD
Director, Office of Intellectual Property & Venture Development
Cincinnati Children's Research Foundation
Mail Location 7032
3333 Burnet Avenue
Cincinnati, Ohio 45229-3039
Phone: 513-636-7695
Fax: 513-636-8453
Email: jdfonda@cchmc.org
| Related Study Information |
|---|
| You must have the free Adobe Acrobat" Reader software installed on your computer to read this file. You can download Adobe Acrobat" Reader at Adobe's web site by selecting the version appropriate for your type of computer. |
