Elevation of RNA-binding protein CUGBP1 is an early event in an inducible heart-specific mouse model of myotonic dystrophy
J. Clin. Invest. Guey-Shin Wang, et al. 117:2802 doi:10.1172/JCI32308 [
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Figure 3Misregulated alternative splicing of
Tnnt2 and
Fxr1h in heart expressing EpA960(R) mRNA but not EpA0(R) mRNA.
(
A) Alternative splicing patterns of mouse
Tnnt2 exons 4 and 5 and the location of the RT-PCR primers (arrows). (
B) Mice expressing EpA960(R) mRNA reverted to the embryonic splicing pattern of
Tnnt2. The EpA960/MCM bitransgenic mice from 3 EpA960 lines as well as transgenic EpA960 and MCM mice were given tamoxifen (T) at a dosage of 20 mg/kg/d for 5 consecutive days, and RNA was extracted 1 week after the last injection. EpA960/MCM bitransgenic littermates treated with oil served as mock (M) controls. E18 cardiac tissue exhibited the
Tnnt2 embryonic alternative splicing pattern. Percent of mRNAs containing exons 4 and 5 is shown. Asterisks denote a hybrid band of the 2 smallest PCR products. (
C) Mice expressing EpA0(R) mRNA exhibited no phenotype and retained adult splicing patterns of
Tnnt2 splicing both 1 week and 1 month following tamoxifen injection. (
D) Decreased inclusion of exons 15 and 16 of
FXR1h in mouse heart expressing EpA960(R) mRNA. Percent of mRNAs containing exons 15 and 16 is shown. (
E) Decreased inclusion of exons 15 and 16 of
FXR1h was also observed in individuals with DM1 (patient identification number shown in parentheses). Splicing abnormalities were not observed in tissue from unaffected individuals or individuals with non-DM1 forms of dilated cardiomyopathy (DCM).
