@prefix this: <http://www.tkuhn.ch/bel2nanopub/RAtmq7pCVm1p46DpTvHSirKvzEWMrc3xXTbSwPxwCYOhQ> .
@prefix sub: <http://www.tkuhn.ch/bel2nanopub/RAtmq7pCVm1p46DpTvHSirKvzEWMrc3xXTbSwPxwCYOhQ#> .
@prefix beldoc: <http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel> .
@prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#> .
@prefix rdf: <http://www.w3.org/1999/02/22-rdf-syntax-ns#> .
@prefix xsd: <http://www.w3.org/2001/XMLSchema#> .
@prefix dct: <http://purl.org/dc/terms/> .
@prefix dce: <http://purl.org/dc/elements/1.1/> .
@prefix pav: <http://purl.org/pav/> .
@prefix np: <http://www.nanopub.org/nschema#> .
@prefix belv: <http://www.selventa.com/vocabulary/> .
@prefix prov: <http://www.w3.org/ns/prov#> .
@prefix Protein: <http://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI_36080> .
@prefix mgi: <http://www.informatics.jax.org/marker/MGI:> .
@prefix geneProductOf: <http://purl.obolibrary.org/obo/RO_0002204> .
@prefix hasPart: <http://purl.obolibrary.org/obo/BFO_0000051> .
@prefix schem: <http://resource.belframework.org/belframework/1.0/namespace/selventa-legacy-chemical-names/> .
@prefix ProteinComplex: <http://amigo.geneontology.org/amigo/term/GO:0043234> .
@prefix go: <http://amigo.geneontology.org/amigo/term/GO:> .
@prefix hasAgent: <http://semanticscience.org/resource/SIO_000139> .
@prefix species: <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=> .
@prefix occursIn: <http://purl.obolibrary.org/obo/BFO_0000066> .
@prefix pubmed: <http://www.ncbi.nlm.nih.gov/pubmed/> .
@prefix orcid: <http://orcid.org/> .

sub:Head {
  this: np:hasAssertion sub:assertion;
    np:hasProvenance sub:provenance;
    np:hasPublicationInfo sub:pubinfo;
    a np:Nanopublication .
}

sub:assertion {
  sub:_1 hasPart: schem:Thyrotropin, sub:_2;
    a ProteinComplex: .
  
  sub:_2 geneProductOf: mgi:98849;
    a Protein: .
  
  sub:_3 hasAgent: sub:_4;
    a go:0005525 .
  
  sub:_4 geneProductOf: mgi:95777;
    a Protein: .
  
  sub:_5 occursIn: species:10090;
    rdf:object sub:_3;
    rdf:predicate belv:directlyIncreases;
    rdf:subject sub:_1;
    a rdf:Statement .
  
  sub:assertion rdfs:label "complex(p(MGI:Tshr),a(SCHEM:Thyrotropin)) => gtp(p(MGI:Gnas))" .
}

sub:provenance {
  beldoc: dce:description "Approximately 61,000 statements.";
    dce:rights "Copyright (c) 2011-2012, Selventa. All rights reserved.";
    dce:title "BEL Framework Large Corpus Document";
    pav:authoredBy sub:_7;
    pav:version "1.4" .
  
  sub:_6 prov:value "Humans expressing one allele of the thyroid transcription factor 1 (TTF1) gene have neurological symptoms and increased serum TSH with variable degrees of hypothyroidism. Ttf1+/- mice have also poor coordination and increased serum TSH concentration (205 +/- 22 vs. 92 +/- 12 mU/liter; P < 0.001) and slightly lower T4 (46 +/- 3 vs. 63 +/- 6 nmol/liter; P < 0.02) as compared with Ttf1+/+ mice. To determine whether the hypothyroidism is of central or primary origin, we examined the bioactivity of TSH, thyroidal response to exogenous TSH and the expression of genes regulated by TTF1. TSH bioactivity was normal, but T4 response to a low but not high dose of TSH was significantly reduced in the Ttf1+/- mice (5.5 +/- 2.2 vs. 15.3 +/- 4.1 nmol/liter; P < 0.03), indicating a reduced thyroidal response. Thyroid mRNAs were measured by real-time PCR (Ttf1+/+ littermates = 100%). Ttf1+/- mice had half the levels of TTF1 mRNA (54 +/- 9; P < 0.01) and protein, confirming their haploinsufficiency. Significantly lower levels of mRNAs were observed for two of the three genes with TTF1 cis elements: TSH receptor (TSHr, 57 +/- 4%; P < 0.002), thyroglobulin (63 +/- 7%; P < 0.005), but not thyroid peroxidase (81 +/- 12%; P > 0.05). No significant difference between the two genotypes was found for Pax8, sodium iodide symporter, and iodothyronine deiodinase 1. These results show that Ttf1 haploinsufficiency causes a reduction in the expression of TSHr and thyroglobulin, genes with TTF1 binding sites in their promoter regions. The low TSHr is only partially compensated by an increase in TSH secretion because T4 remains mildly reduced. However, administration of a larger amount of TSH obliterates the response differences by saturating a reduced amount of receptor.";
    prov:wasQuotedFrom pubmed:12907760 .
  
  sub:_7 rdfs:label "Selventa" .
  
  sub:assertion prov:hadPrimarySource pubmed:12907760;
    prov:wasDerivedFrom beldoc:, sub:_6 .
}

sub:pubinfo {
  this: dct:created "2014-07-03T14:30:15.440+02:00"^^xsd:dateTime;
    pav:createdBy orcid:0000-0001-6818-334X, orcid:0000-0002-1267-0234 .
}