| First Author | Ruiz-Lozano P | Year | 1998 |
| Journal | Development | Volume | 125 |
| Issue | 3 | Pages | 533-44 |
| PubMed ID | 9425147 | Mgi Jnum | J:46220 |
| Mgi Id | MGI:1197375 | Doi | 10.1242/dev.125.3.533 |
| Citation | Ruiz-Lozano P, et al. (1998) Energy deprivation and a deficiency in downstream metabolic target genes during the onset of embryonic heart failure in RXRalpha-/- embryos. Development 125(3):533-44 |
| abstractText | RXR alpha null mutant mice display ocular and cardiac malformations, liver developmental delay, and die from cardiac failure around embryonic day (E) 14.5 pc. To dissect the molecular basis of the RXR alpha-associated cardiomyopathy, we performed subtractive hybridization and systematically characterized putative downstream target genes that were selectively lacking in the mutant embryos, both at early (E10.5) and late (E13.5) stages of mouse embryonic development. Approximately 50% of the subtracted clones (61/115) encoded proteins involved in intermediary metabolism and electron transport, suggesting an energy deficiency in the RXR alpha(-/-) embryos. In particular, clone G1, which encodes subunit 14.5b of the NADH- ubiquinone dehydrogenase complex, displayed a dose- dependent expression in the wild-type, heterozygous and RXR alpha mutant mice. This gene was also downregulated in a retinoid-deficient rat embryo model. ATP content and medium Acyl-CoA dehydrogenase mRNA were lower in RXR alpha mutant hearts compared to wild-type mice. Ultrastructural studies showed that the density of mitochondria per myocyte was higher in the RXR alpha mutant compared to wild-type littermates. We propose a model whereby defects in intermediary metabolism may be a causative factor of the RXR alpha(-/-) phenotype and resembles an embryonic form of dilated cardiomyopathy. |
