research animal models

ORIGIN
The 11BHSD2 mouse was produced by injection of a construct, containing 11β-HSD2 cDNA isolated from mouse kidney and cloned into plasmid Clone 26 to recruit the 5.4 kb mouse α–myosin heavy chain (α-MHC) promoter, into pronuclei of C57BL/6 embryos. Transgenic mice were maintained by sibling mating and used as hemizygotes. Transferred to Charles River under exclusive license from Pfizer, Inc., in 2011.

STRAIN CODE
Coming Soon

COAT COLOR
Black

MUTATION INFORMATION
This model was developed to evaluate the role of aldosterone in cardiac pathophysiology by producing over expression of 11β-HSD2 in cardiac myocytes, leading to aldosterone selectivity in these cells. In one founder line (326).
Key features of this model include:

• The highest levels of 11β-HSD2 are found in the heart with accompanying low-level induction in the lung, liver, spleen, brain and skeletal muscle, but no induction is observed in the kidney and colon;
• Premature death at 4-6 months of age from progressive heart failure;
• Postmortem evaluation showed pleural effusions and significant enlargement of all four chambers of the heart;
• Cardiomyocyte hypertrophy accompanied by extensive interstitial fibrosis was seen on histological examination;
• No involvement of cardiac arteries suggesting selectivity of the model;
• Eplerenone (200mg/kg/day in feed from 1-3.5 months of age) ameliorates the effects of over expression of 11β-HSD2

Aldosterone is known to regulate blood pressure and blood volume via unidirectional transepithelial sodium transport. Additionally, other direct roles of aldosterone in the cardiovascular system have been postulated. In experimental models of hypertension, aldosterone produces blood pressure elevation by stimulating brain mineralocorticoid receptors (MRs), and when combined with high salt intake, produces cardiac hypertrophy, fibrosis and vascular inflammation injury independent of blood pressure elevation. Expression of 11β-hydroxysteroid dehydrogenase type 2, an enzyme found in various epithelial cells and vascular smooth muscle cells, converts endogenous glucocorticoid to their 11-keto forms, which are receptor-inactive, thereby conferring selectivity towards aldosterone to these cells. In cardiac myocytes, the endogenous levels of 11β-HSD2 is low and, thus, aldosterone plays only a minor role in activation of MRs under normal physiological conditions.

RESEARCH APPLICATION
Cardiac Hypertrophy, Heart Failure

ADDITIONAL INFORMATION
For additional information about 11BHSD2 mice, please contact us at info@eu.crl.com.

DISCLAIMER
11BHSD2 mice may be subject to the licensed patents and are sold only for research purposes under agreement from Pfizer, Inc.