RGD Reference Report - Quantitative Trait Loci Associated with Elevated TSH in the Wistar-Kyoto Rat. - Rat Genome Database

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Quantitative Trait Loci Associated with Elevated TSH in the Wistar-Kyoto Rat.

Authors: Baum, AE  Solberg, LC  Kopp, P  Ahmadiyeh, N  Churchill, G  Takahashi, JS  Jameson, JL  Redei, EE 
Citation: Baum AE, etal., Endocrinology 2004 Oct 28;.
RGD ID: 1302891
Pubmed: PMID:15514085   (View Abstract at PubMed)
PMCID: PMC3764449   (View Article at PubMed Central)
DOI: DOI:10.1210/en.2004-0948   (Journal Full-text)

Thyroid hormones are essential for the regulation of developmental and physiologic processes. The genetic factors underlying naturally occurring variability in mammalian thyroid function are, however, only partially understood. Genetic control of thyroid function can be studied with animal models such as the inbred Wistar-Kyoto (WKY) rat strain. Previous studies established that WKYs have elevated TSH, slightly elevated total T3, and normal total T4 levels compared with Wistar controls. The present study confirmed a persistent 24 h elevation of TSH in WKYs compared with the Fisher 344 (F344) rat, another inbred strain. Acute T3 challenge (25 microg/100 g body weight ip) suppressed serum TSH and T4 levels in both strains. Quantitative trait locus analysis of elevated TSH in a reciprocally bred WKYxF344 F2 population identified one highly significant locus on chromosome 6 (LOD=11.7, TSH-1) and one suggestive locus on chromosome 5 (LOD=2.3, TSH-2). The confidence interval of TSH-1 contains the TSH receptor and Type 2 deiodinase genes, and TSH-2 contains the Type 1 deiodinase gene. The WKY alleles of each gene contain sequence alterations but further studies are indicated to identify the specific gene or genes responsible for altered regulation of the thyroid axis. These findings suggest that one or more genetic alterations within the TSH-1 locus significantly contribute to the altered thyroid function tests of the WKY rat.



Disease Annotations    Click to see Annotation Detail View
RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Thshl1Ratthyroid gland disease  IAGP  RGD 
Thshl2Ratthyroid gland disease  IAGP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Thshl1Ratincreased circulating thyroid-stimulating hormone level  IAGP  RGD 
Thshl2Ratincreased circulating thyroid-stimulating hormone level  IAGP  RGD 
WKY/NHsdRatincreased thyroid-stimulating hormone level  IAGP compared to F344/NHsdRGD 

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Rat Strains:
Clinical Measurements:
Experimental Conditions:
Measurement Methods:
Objects Annotated

QTLs
Thshl1  (Thyroid stimulating hormone level QTL 1)
Thshl2  (Thyroid stimulating hormone level QTL 2)

Strains
F344/NHsd  (F344/NHsd)
WKY/NHsd  (NA)


Additional Information