Ttntm1Brge mice

Challenge

Lack of accurate animal models to study human Dilated Cardiomyopathy (DCM)

Solution

A mouse model that recapitulates a Titin truncation mutation (c.43628insAT), previously identified in a large family with autosomal dominant DCM characterized by ventricular dilatation and systolic dysfunction. It provides a unique platform to test drugs that prevent the onset of symptoms such as gene therapy.

Technology 

• When chronically exposed to angiotensin II or isoproterenol, heterozygous mice developed marked left ventricular dilatation with impaired fractional shortening and diffuse myocardial fibrosis.
• This model mimics typical features of human dilated cardiomyopathy and allows to study of how titin mutations and their repair affect cardiac function and remodel the heart.

Publications

Stress-induced dilated cardiomyopathy in a knock-in mouse model mimicking human titin-based disease
Journal of Molecular and Cellular Cardiology. (2009) 47 (3), 352 – 358.

Lab

Animal Phenotyping Platform

Arnd Heuser