Disease relevance of Tpo

• Transformation of rat thyroid cells with polyoma virus middle T antigen results in loss of the thyroid-differentiated phenotype, measured as the expression of the thyroglobulin (Tg), thyroperoxidase (TPO), and sodium/iodide symporter (NIS) genes [1].
• These findings suggested that the dwarf mutation caused a primary congenital hypothyroidism by TPO deficiency, resulting in a defect of thyroid hormone synthesis [2].
• A Novel Hypothyroid Dwarfism Due to the Missense Mutation Arg479Cys of the Thyroid Peroxidase Gene in the Mouse [2].
• Development of a murine model of autoimmune thyroiditis induced with homologous mouse thyroid peroxidase [3].
• None of the control mice injected with the purified fusion partner developed anti-TPO antibodies and thyroiditis [3].

High impact information on Tpo

• Expression of thyroglobulin (Tg) and thyroperoxidase (TPO) genes in thyroid follicular cells occurs in the mouse at embryonic day (E)14 [4].
• Raf-1 is not required for megakaryocytopoiesis or TPO-induced ERK phosphorylation [5].
• Murine TPO stimulated mouse megakaryocyte progenitor development [6].
• To address whether TPO affects very primitive hematopoietic progenitors, we studied the residual cells from the BMs of mice treated with high doses of 5-fluorouracil [6].
• We discuss the relevance of our results to the reported defects of TpoR processing in myeloproliferative diseases and to the mechanisms of Tpo signaling and clearance via the TpoR [7].

Chemical compound and disease context of Tpo

• The effect resulted in decreases in serum levels of 3,5,3'-triiodothyronine (T3) and thyroxine (T4), and slight increases in serum 3,3',5'-triiodothyronine (rT3) levels and thyroid weight, but no difference in the values for the body-weight gain, serum thyroid stimulating hormone (TSH) levels and thyroid peroxidase (TPO) activities [8].

Biological context of Tpo

• We report in this paper the cloning of TTF-2, a DNA binding protein that recognizes sites on both Tg and TPO promoters [4].
• In the thyroid, TTF-2 expression is down-regulated just before the onset of Tg and TPO gene expression, suggesting that this transcription factor plays the role in development of a negative controller of thyroid-specific gene expression [4].
• A recombinant autoantibody Fab (SP1.4) to thyroid peroxidase (TPO), cloned from intrathyroidal B cell immunoglobulin genes, interacts with an epitope on TPO recognized by all patients with autoimmune thyroid disease [9].
• Nucleotide sequence of the cDNA encoding mouse thyroid peroxidase [10].
• The TPO cDNA is 3281 nt long and its open reading frame encodes a protein composed of 914 amino acids (aa), including a putative initiation Met [10].

Anatomical context of Tpo

• No specific 51Cr release was observed when either fibroblasts or Chinese hamster ovary cells expressing cell surface TPO were used as target cells [9].
• Together, these data indicate that IgG1-SP/TPO complexes bind to either Fc gamma RI on monocytes or RIII on natural killer cells [9].
• The FRTL-5/TA cell line was the least differentiated one as thyroglobulin mRNA was detectable in only minute amounts and thyroid peroxidase expression could not be measured [11].
• Autoantibodies and autoreactive T lymphocytes to TPO are believed to play a major role in the pathogenesis of lymphocytic thyroiditis [3].
• Draining lymph node cells from rmTPO-immunized animals showed dose-dependent proliferation to TPO stimulation [3].

Associations of Tpo with chemical compounds

• Sequencing of the Tpo gene of the dwarf mice demonstrated a C to T substitution at position 1508 causing an amino acid change from arginine (Arg) to cysteine (Cys) at codon 479 (Arg479Cys) [2].
• In contrast, a neutralizing alpha4beta1 monoclonal antibody blocked TPO-induced MK growth, and an integrin alpha4beta1 ligand, the H296 fragment of fibronectin, enhanced MK growth at all concentrations of TPO [12].
• A contemporary example of a chemical acting as TPO-inhibitor is sulfamethazine [13].
• It increased serum cholesterol, TPO and T4 activity [14].
• Effects of rose bengal on serum levels of thyroid hormones and thyroid peroxidase activity in male mice [8].

Other interactions of Tpo

• These recent studies position cpk within 1.3 cM of D12Nyu2, closely flanked by (Odc, D12Mit10) and (Tpo, D12Mit12) [15].
• Treatments with Tpo also reduced the level of the chemokine KC in plasma and the level of expression of mRNA for inflammatory and coagulation proteins in the lungs of irradiated mice [16].
• Hydrazone compounds described here as thrombopoietin receptor agonists were identified as activating STAT proteins in a Tpo responsive cell line [17].
• This result supports the hypothesis of the presence of two distinct populations of MK progenitors: IL-3-dependent and Tpo-dependent [18].
• One sequence, TIWLREHNRV (residues 303-312 of the sheep enzyme), is very closely related to the sequence TLW(L)LREHNRL common to thyroid peroxidase and myeloperoxidase [19].

Analytical, diagnostic and therapeutic context of Tpo

• Cells secreting TPO autoantibodies were cloned, and IgG1-SP and IgG4-SP were affinity purified from medium using protein G. Their subclass specificities were confirmed by enzyme-linked immunosorbent assay and fluorometry after binding to Chinese hamster ovary cells expressing cell surface TPO [9].
• Gene mapping revealed that the dwarf mutation was closely linked to the thyroid peroxidase (Tpo) gene on chromosome 12 [2].
• Western blotting revealed that TPO protein of the dwarf mice was detected in a microsomal fraction of thyroid tissue, but peroxidase activity was not detected [2].
• Identification of T cell epitopes of TPO may enable the development of immunotherapy to prevent chronic hypothyroidism in AT [20].

References