RXRalpha overexpression in cardiomyocytes causes dilated cardiomyopathy but fails to rescue myocardial hypoplasia in RXRalpha-null fetuses
| Autor: | Philippe Kastner, Manuel Mark, Nadia Messadeq, Pierre Rustin, Vemparala Subbarayan, Pierre Chambon |
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| Rok vydání: | 2000 |
| Předmět: |
Genetically modified mouse
Heart Defects Congenital medicine.medical_specialty Receptors Retinoic Acid Transgene Respiratory chain Mice Transgenic Retinoid X receptor Biology Article Mice Internal medicine medicine Myocyte Animals Fetus Gene Expression Regulation Developmental Dilated cardiomyopathy General Medicine medicine.disease Hypoplasia DNA-Binding Proteins Endocrinology Retinoid X Receptors Cardiomyopathies Transcription Factors |
| Zdroj: | The Journal of clinical investigation. 105(3) |
| ISSN: | 0021-9738 |
| Popis: | Retinoid X receptor α‐null (RXRα-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 RXRα in mutant cardiac myocytes could rescue these defects. Two transgenic mouse lines specifically overexpressing an RXRα protein in cardiomyocytes were generated, using the cardiac α-myosin heavy chain (α-MHC) promoter. Breeding the high copy number transgenic line onto an RXRα-null genetic background did not prevent the myocardial hypoplasia and fetal lethality associated with the RXRα‐/‐ genotype, even though the transgene was expressed in the ventricles as early as 10.5 days post-coitum. These data suggest that the RXRα function involved in myocardial growth may correspond to a non‐cell-autonomous requirement for a signal 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. J. Clin. Invest. 105:387‐394 (2000). |
| Databáze: | OpenAIRE |
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