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<article><div class="banner banner--gray banner--compact" style="--banner-background-image: url('/sites/default/files/media/image/2021-03/2015.jpg');--banner-background-focus: 50% 50%"><div class="banner__wrapper"><div class="banner__container"><h2 class="banner__heading">NIH Research Festival</h2><div class="banner__content"><p><strong><time datetime="2015-09-16">September 16</time> – <time datetime="2015-09-18">18, 2015</time></strong></p></div></div></div></div></article>
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<div class="section"><div data-drupal-messages-fallback class="hidden"></div></div><main role="main"><div id="main-content" tabindex="-1"></div><div class="section"><div class="content-sidebar"><div class="content-sidebar__main"><div class="content-sidebar__main-content"><div id="block-mainpagecontent-2"><article><h1>Thyroid Hormone Receptor α1 Mutants Impair Erythropoiesis</h1><div class="schedule"><div class="schedule__label"><div class="schedule__label-text"><time datetime="2015-09-18">Friday, September 18, 2015</time>
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– Poster Session IV
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</div></div><div class="schedule__content"><div class="schedule__item"><div class="schedule__time">12:00 – 1:30 p.m.</div><div class="schedule__description"><p><strong>FAES Terrace</strong></p></div><div class="schedule__description"><p><strong>NCI</strong></p></div><div class="schedule__description"><p><strong>GEN-34</strong></p></div></div></div></div><p><strong>FARE Award Winner</strong></p><h2>Authors</h2><ul><li>SM Park</li><li>JW Park</li><li>CR Han</li><li>Li Zhao</li><li>D Bodine</li><li>SH Cheng</li></ul><h2>Abstract</h2><p>The genomic signaling by thyroid hormone (T3) in growth, development, and metabolic homeostasis is via thyroid hormone receptors (TRs). Patients with mutations of the THRA gene exhibit classical features of hypothyroidism, including decreased red blood cell mass and anemia. The molecular mechanism by which T3 via TRalpha1 regulates erythropoiesis is yet to be elucidated. We have created a mutant mouse expressing a mutated TRalpha1 (denoted as PV; Thra1PV/+ mouse) that shares the same mutated C-terminal sequence (-TLPRGL) as in patients with mutated TRalpha1. In the present studies, we used Thra1PV/+ mice to explore how TRalpha1 mutants act to cause abnormalities in erythropoiesis. Consistent with observations in patients, erythropoietic parameters such as red blood cell counts, hemoglobin content, and hematocrit levels were significantly lower in Thra1PV/+ mice than wild type mice. Total bone marrow cells of Thra1PV/+ mice were significantly reduced (64%). In addition, erythrocytic progenitors were markedly reduced, resulting in impaired erythropoiesis in Thra1PV/+ mice. Importantly, the impaired erythrocytic progenitors were partially rescued by T3 treatment. The expression of two key regulators of erythropoiesis, GATA-1 and KLF1, was decreased in the spleen and bone marrow cells of Thra1PV/+ mice. These results indicate that TRalpha1PV could impair erythropoiesis via repression of these two critical erythrocytic genes. Taken together, these data provide new insights into how TRalpha1 mutants act to cause hematopoietic disorders in patients with mutations of the THRA gene. Importantly, the Thra1PV/+ mouse could serve as a preclinical mouse model to identify novel molecular targets for treatment of hematopoietic disorders.</p><p><strong>Scientific Focus Area</strong>: Genetics and Genomics</p><p class="updated"><small>This page was last updated on Friday, March 26, 2021</small></p></article>
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