| First Author | Lübkemeier I | Year | 2015 |
| Journal | Circ Cardiovasc Genet | Volume | 8 |
| Issue | 1 | Pages | 21-9 |
| PubMed ID | 25504652 | Mgi Jnum | J:228567 |
| Mgi Id | MGI:5707819 | Doi | 10.1161/CIRCGENETICS.114.000793 |
| Citation | Lubkemeier I, et al. (2015) Human Connexin43E42K mutation from a sudden infant death victim leads to impaired ventricular activation and neonatal death in mice. Circ Cardiovasc Genet 8(1):21-9 |
| abstractText | BACKGROUND: Sudden infant death syndrome (SIDS) describes the sudden, unexplained death of a baby during its first year of age and is the third leading cause of infant mortality. It is assumed that </=20% of all SIDS cases are because of cardiac arrhythmias resulting from mutations in ion channel proteins. Besides ion channels also cardiac gap junction channels are important for proper conduction of cardiac electric activation. In the mammalian heart Connexin43 (Cx43) is the major gap junction protein expressed in ventricular cardiomyocytes. Recently, a novel Connexin43 loss-of-function mutation (Cx43E42K) was identified in a 2-month-old SIDS victim. METHODS AND RESULTS: We have generated Cx43E42K-expressing mice as a model for SIDS. Heterozygous cardiac-restricted Cx43E42K-mutated mice die neonatally without major cardiac morphological defects. Electrocardiographic recordings of embryonic Cx43+/E42K mice reveal severely disturbed ventricular activation, whereas immunohistochemical analyses show normal localization and expression patterns of gap junctional Connexin43 protein in the Cx43E42K-mutated newborn mouse heart. CONCLUSIONS: Because we did not find heterogeneous gap junction loss in Cx43E42K mouse hearts, we conclude that the Cx43E42K gap junction channel creates an arrhythmogenic substrate leading to lethal ventricular arrhythmias. The strong cardiac phenotype of Cx43E42K expressing mice supports the association between the human Cx43E42K mutation and SIDS and indicates that Connexin43 mutations should be considered in future studies when SIDS cases are to be molecularly explained. |
