Differential display and cloning of thyroid hormone-regulated mRNAs in human fibroblasts evidence for c-erbA[beta]1-receptor-specific modulation of the Na, K-ATPase BETA1 subunit gene / by Lance D. Miller.
| Author/creator | Miller, Lance D. author. |
| Other author | Usala, Stephen J., degree supervisor. |
| Other author | East Carolina University. Department of Biology. |
| Format | Theses and dissertations |
| Production | 1995. |
| Description | iv, 67 leaves : illustrations ; 28 cm |
| Supplemental Content | Access via ScholarShip |
| Subjects |
| Summary | Thyroid hormone (T3: 3,5,3'-triiodothyronine) action is mediated through high affinity nuclear receptor proteins that modulate transcription of target genes. At certain loci the predominant receptor isoforms of man, c-erbAALPHA1 and c-erbABETA1, have the capacity to bind T3 and modulate gene expression in a similar manner. However, tissue-specific and development-dependent distributions of the BETA1- and ALPHA1-receptors suggest separate physiologic roles. Functional differences between receptor isoforms have yet to be defined as the data on isoform-specific function is sparse. Two genetic defects associated with generalized resistance to thyroid hormone (GRTH) offer a unique opportunity to study isoform-specific gene expression as well as GRTH pathology. The Refetoff patient is homozygous for a deleted BETA receptor whereas the Bercu patient is homozygous for a mutant BETA-receptor that lacks T3 binding ability and thus antagonizes normal receptor function (dominant negative effect). In both patients, the ALPHA1-receptor alone is presumably responsible for normal modulation of T3-regulated genes. Using the differential display technique (DIFFDIS) we isolated and cloned a number of cDNA tags corresponding to T3-regulated mRNAs expressed in Bercu, Refetoff, and normal fibroblasts. One such tag was sequenced and identified as the 3'-untranslated region of the Na,K-ATPase Beta1 subunit gene (NAK). The DIFFDIS pattern of NAK expression showed strong T3 induction in normal cells versus little or no T3 induction in Bercu and Refetoff fibroblasts suggesting, for the first time, that NAK expression may be pi-isoform-specific. |
| General note | Submitted to the faculty of the Department of Biology. |
| General note | Advisor: Stephen J. Usala |
| Dissertation note | M.S. East Carolina University 1995 |
| Bibliography note | Includes bibliographical references (leaves 58-67). |
| Genre/form | dissertations. |
| Genre/form | Academic theses. |
| Genre/form | Academic theses. |
| Genre/form | Thèses et écrits académiques. |
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