| First Author | Subbarayan V | Year | 2000 |
| Journal | J Clin Invest | Volume | 105 |
| Issue | 3 | Pages | 387-94 |
| PubMed ID | 10675365 | Mgi Jnum | J:60351 |
| Mgi Id | MGI:1353197 | Doi | 10.1172/JCI8150 |
| Citation | Subbarayan V, et al. (2000) RXRalpha overexpression in cardiomyocytes causes dilated cardiomyopathy but fails to rescue myocardial hypoplasia in RXRalpha-null fetuses. J Clin Invest 105(3):387-94 |
| abstractText | Retinoid X receptor alpha-null (RXRalpha-null) mutants exhibit hypoplasia of their ventricular myocardium and die at the fetal stage. In the present study, we wished to determine whether transgenic re-expression of RXRalpha in mutant cardiac myocytes could rescue these defects. Two transgenic mouse lines specifically overexpressing an RXRalpha protein in cardiomyocytes were generated, using the cardiac alpha-myosin heavy chain (alpha-MHC) promoter. Breeding the high copy number transgenic line onto an RXRalpha-null genetic background did not prevent the myocardial hypoplasia and fetal lethality associated with the RXRalpha(-/-) genotype, even though the transgene was expressed in the ventricles as early as 10. 5 days post-coitum. These data suggest that the RXRalpha function involved in myocardial growth may correspond to a non-cell-autonomous requirement forsignal orchestrating the growth and differentiation of myocytes. Interestingly, the adult transgenic mice developed a dilated cardiomyopathy, associated with myofibrillar abnormalities and specific deficiencies in respiratory chain complexes I and II, thus providing an additional model for this genetically complex disease. |
