Probing the genetic basis for thyrotropin receptor antibodies and hyperthyroidism in immunized CXB recombinant inbred mice

Holly A. Aliesky, Pavel N. Pichurin, Chun Rong Chen, Robert Williams, Basil Rapoport, Sandra M. McLachlan

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Immunization with adenovirus encoding the TSH receptor (TSHR) or its A-subunit induces Graves' hyperthyroidism in BALB/c and BALB/c x C57BL/6 offspring but not C57BL/6 mice. High-resolution genetic maps are available for 13 recombinant inbred CXB strains generated from BALB/c x C57BL/6 progeny by repeated brother x sister matings to establish fully inbred lines. CXB strains were studied before and after A-subunit adenovirus immunization for TSHR antibodies (TBI, inhibition of TSH binding), serum T4, and thyroid histology. All strains developed TBI activity (at variable levels), six strains became hyperthyroid, and one was overtly thyrotoxic. No low TBI responders became hyperthyroid, but high TBI did not predict hyperthyroidism. Preimmunization T4 levels varied in different CXB strains and was unrelated to subsequent T4 elevation. Linkage analysis indicated that different chromosomes were involved in generating TSHR antibodies and serum T4 before and after immunization. TBI activity was linked in part with major histocompatibility (MHC) genes on chromosome 17 (Chr 17) but induced Graves' disease involved non-MHC genes (Chr 19 and 10). The Chr 10 locus is close to the Trhde gene that encodes TSH-releasing hormone degrading enzyme. Expression of Trhde is controlled by thyroid hormones and linkage with a thyroid function-related gene is intriguing. Our data, the first genome scan in murine Graves' disease, provides insight into the role of MHC and non-MHC genes in human and murine Graves' disease. Finally, our study demonstrates the potential of recombinant inbred mice for discriminating between immune-response genes and thyroid function susceptibility genes in Graves' disease.

Original languageEnglish (US)
Pages (from-to)2789-2800
Number of pages12
JournalEndocrinology
Volume147
Issue number6
DOIs
StatePublished - Jun 1 2006

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Thyrotropin Receptors
Hyperthyroidism
Histocompatibility
Graves Disease
Antibodies
Genes
Immunization
Thyroid Gland
Adenoviridae
Chromosomes, Human, Pair 17
Serum
Thyroid Hormones
Inbred C57BL Mouse
Histology
Chromosomes
Genome
Hormones
Enzymes

All Science Journal Classification (ASJC) codes

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Probing the genetic basis for thyrotropin receptor antibodies and hyperthyroidism in immunized CXB recombinant inbred mice. / Aliesky, Holly A.; Pichurin, Pavel N.; Chen, Chun Rong; Williams, Robert; Rapoport, Basil; McLachlan, Sandra M.

In: Endocrinology, Vol. 147, No. 6, 01.06.2006, p. 2789-2800.

Research output: Contribution to journalArticle

Aliesky, Holly A. ; Pichurin, Pavel N. ; Chen, Chun Rong ; Williams, Robert ; Rapoport, Basil ; McLachlan, Sandra M. / Probing the genetic basis for thyrotropin receptor antibodies and hyperthyroidism in immunized CXB recombinant inbred mice. In: Endocrinology. 2006 ; Vol. 147, No. 6. pp. 2789-2800.
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