| First Author | Gloss B | Year | 1999 |
| Journal | Endocrinology | Volume | 140 |
| Issue | 2 | Pages | 897-902 |
| PubMed ID | 9927321 | Mgi Jnum | J:52905 |
| Mgi Id | MGI:1330647 | Doi | 10.1210/endo.140.2.6527 |
| Citation | Gloss B, et al. (1999) Altered cardiac phenotype in transgenic mice carrying the delta337 threonine thyroid hormone receptor beta mutant derived from the S family. Endocrinology 140(2):897-902 |
| abstractText | The heart has been recognized as a major target of thyroid hormone action. Our study investigates both the regulation of cardiac-specific genes and contractile behavior of the heart in the presence of a mutant thyroid hormone receptor beta 1 (T3R beta 1-Delta 337T) derived from the S kindred. The mutant receptor was originally identified in a patient with generalized resistance to thyroid hormone. Cardiac expression of the mutant receptor was achieved by a transgenic approach in mice. As the genes for myosin heavy chains (MHC alpha and MHC beta) and the cardiac sarcoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA2) are known to be regulated by T-3, their cardiac expression was analyzed. The messenger RNA levels for MHC alpha and SERCA2 were markedly down-regulated, MHC beta messenger RNA was up-regulated. Although T-3 levels were normal in these animals, this pattern of cardiac gene expression mimics a hypothyroid phenotype. Cardiac muscle contraction was significantly prolonged in papillary muscles from transgenic mice. The electrocardiogram of transgenic mice showed a substantial prolongation of the QRS interval. Changes in cardiac gene expression, cardiac muscle contractility, and electrocardiogram are compatible with a hypothyroid cardiac phenotype despite normal T-3 levels, indicating a dominant negative effect of the T3R beta mutant. |
