Titin-eGFP and Titin-DsRed mice

Challenge

Titin is the largest known human protein and is crucial for muscle contraction. It is involved in a variety of cardiac and skeletal muscle disorders such as dilated cardiomyopathy, diastolic heart failure and muscular dystrophy. This giant sarcomeric protein has a size of up to 3.7 MDa. Titin is therefore not readily available for overexpression, gain-of-function studies, or the generation of a tagged full-length protein.

Solution

These titin-eGFP and Titin-Dsred knock-in mice are the only two available rodent models that allow live visualization of titin dynamics and remodeling. They can also be used for tracking of implanted cells to monitor the efficiency of cell therapies.

Technology 

• Reporter DsRed integrated into titin’s Z‑disk exon 28 
• Reporter eGFP into titin’s M‑band exon 6
• No apparent adverse phenotype in homozygous or heterozygous animals

Development status

• Double heterozygous animals with titin labeled at the Z‑disk and M‑band can be obtained by crossing homozygous titin-DsRed(Z) mice with the homozygous titin-eGFP(M) mice
• This dual fluorescent model allows to discriminate titin’s N and C termini and has been used to study sarcomere dynamics

Publications

Titin visualization in real time reveals an unexpected level of mobility within and between sarcomeres
J Cell Biol (2011) 193 (4): 785 – 798.

Resolving titin’s lifecycle and the spatial organization of protein turnover in mouse cardiomyocytes
Proc. Natl. Acad. Sci. U.S.A. (2019) 116, 25126 – 25136.

Lab

Gotthardt Lab

Translational Cardiology and Functional Genomics