B6;FVB-Tg(Myh6/NFAT-luc)1Jmol/J

Stock number: 013781
Research areas: Research Tools

Description

The NFAT-luc transgene has luciferase expression directed by a Myh6/NFAT hybrid promoter (composed of a minimal mouse alpha myosin heavy chain cardiac promoter [Myh6] with upstream copies of the nuclear factor of activated T cell binding site sequence [NFAT; from the mouse interleukin 4 (Il4) promoter]). In the hearts of adult NFAT-luc transgenic mice, NFAT-luc activity is upregulated during pathological cardiac hypertrophy induced by pressure-overload; more dramatically following myocardial infarction-induced heart failure. These NFAT-luc transgenic mice are a reporter of calcineurin-NFAT signaling, and may be useful in studying cardiac hypertrophy and calcineurin/NFAT coupling.

Detailed description

These nuclear factor of activated T cell (NFAT)-luciferase transgenic mice display detectable luciferase activity in most tissues surveyed at 3 weeks of age, with highest expression occurring in brain, kidney, and heart - each of which are sites of considerable calcineurin (Ppp3ca, protein phosphatase 3, catalytic subunit, alpha isoform) protein expression. NFAT-luciferase activity peaks during developmental maturation of the heart, whereas the adult heart shows relatively lower activity. In the adult heart, NFAT-luciferase activity is upregulated in a delayed, but sustained manner throughout 8 weeks of pathological cardiac hypertrophy induced by pressure-overload, or more dramatically following myocardial infarction-induced heart failure. This strain may be useful in studies of cardiac hypertrophy and calcineurin/NFAT coupling.

Development

Nine copies of an NFAT binding site from the mouse Il4 (interleukin 4) promoter (5'-TGGAAAATT-3') were positioned 5' to a minimal Myh6 (myosin, heavy polypeptide 6, cardiac muscle, alpha) promoter and inserted upstream of a luciferase reporter. The transgene was injected into FVB fertilized oocytes. This strain was backcrossed to C57BL/6 for four generations by the donating laboratory.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. 15 markers on 12 chromosomes were found to be segregating, suggesting an incomplete backcross.

Allele

Symbol: Tg(Myh6/NFAT-luc)1Jmol
Name: transgene insertion 1, Jeffery D Molkentin
MGI accession ID: MGI:3851596
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(Myh6/NFAT-luc)1Jmol
Marker name: transgene insertion 1, Jeffery D Molkentin
Chromosome: UN
Strain of origin: FVB
Expressed genes: luc,luciferase,firefly
Site of expression: Luciferase expression is seen in the heart.
Molecular note: Nine copies of a nuclear factor of activated T cell (NFAT) binding site (5'-TGGAAAATT-3') from the interleukin 4 (Il4) promoter were placed 5' to a mouse alpha myosin heavy chain (Myh6) and upstream of a luciferase promoter.