| First Author | Ding JH | Year | 2004 |
| Journal | EMBO J | Volume | 23 |
| Issue | 4 | Pages | 885-96 |
| PubMed ID | 14963485 | Mgi Jnum | J:88432 |
| Mgi Id | MGI:3033268 | Doi | 10.1038/sj.emboj.7600054 |
| Citation | Ding JH, et al. (2004) Dilated cardiomyopathy caused by tissue-specific ablation of SC35 in the heart. EMBO J 23(4):885-96 |
| abstractText | Many genetic diseases are caused by mutations in cis-acting splicing signals, but few are triggered by defective trans-acting splicing factors. Here we report that tissue-specific ablation of the splicing factor SC35 in the heart causes dilated cardiomyopathy (DCM). Although SC35 was deleted early in cardiogenesis by using the MLC-2v-Cre transgenic mouse, heart development appeared largely unaffected, with the DCM phenotype developing 3-5 weeks after birth and the mutant animals having a normal life span. This nonlethal phenotype allowed the identification of downregulated genes by microarray, one of which was the cardiac-specific ryanodine receptor 2. We showed that downregulation of this critical Ca(2+) release channel preceded disease symptoms and that the mutant cardiomyocytes exhibited frequency-dependent excitation-contraction coupling defects. The implication of SC35 in heart disease agrees with a recently documented link of SC35 expression to heart failure and interference of splicing regulation during infection by myocarditis-causing viruses. These studies raise a new paradigm for the etiology of certain human heart diseases of genetic or environmental origin that may be triggered by dysfunction in RNA processing. |
