The Transgenic Animals and Instrumentation Core Facility provides transgenic rats to investigators at Wake Forest School of Medicine and other research facilities.
- (mRen2)27 TG, mRen2.Lewis TG, TGR(ASrAogen) and Hannover SD rats are available to investigators for research purposes. These TG rats have genetic alterations of the renin-angiotensin system.
- (mRen2)27 TG – Originally developed by Drs. Mullins and Ganten (Nature 344:541-544, 1990) in Germany, these rats incorporate the mouse renin-2 gene into the rat genome, and it is expressed on an outbred Hannover Sprague-Dawley (SD) background. Homozygous (mRen2)27 TG rats are bred with Hannover SD rats to produce hemizygous (mRen2)27 TG rats that are made available for research purposes.
- The hemizygous (mRen2)27 TG rat typically develops hypertension as the rats attain sexual maturity, and the hypertension is more extreme in males than females. The hypertension in offspring can be reversed by treatment with an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II AT1 receptor antagonist (AT1 ARB).
- mRen2.Lewis TG – Derived by backcrossing the original (mRen2)27 TG rat with Lewis rats, the mRen2.Lewis TG rat expresses the mRen2 gene on a genetically homogenous Lewis background. Homozygous mRen2.Lewis TG rats can be crossed with Lewis rats to produce hemizygous mRen2.Lewis TG rats, which also show hypertension that is more extreme in males than females and elevated blood pressure that can be reversed by treatment with an ACE inhibitor.
- TGR(ASrAogen) – Also developed by Ganten and colleagues (PNAS 96:3975-3980, 1999), this rat has an antisense to angiotensinogen (Aogen) that is driven by an astrocyte-specific promoter, assuring suppression of Aogen restricted to glial cells of the central nervous system. They have a modestly lower blood pressure, approximately 90 percent reduction in the production of Aogen in the brain but no alteration in Aogen synthesis in the liver or other tissues, and a mild form of diabetes insipidus. Drs. Kasper and Diz have also determined that the TGR(ASrAogen) do not develop insulin resistance; they have a significantly lower body weight as they age; and they exhibit superior cognitive function as they age.
- Hannover SD – These rats serve as the control lines and breeder colonies.
Jasmina Varagic, MD, PhD
Associate Professor, Surgery Hypertension