We have located links that may give you full text access.
A mouse TSH receptor A-subunit transgene expressed in thyroiditis-prone mice may provide insight into why Graves' disease only occurs in humans.
BACKGROUND: Graves' disease, caused by autoantibodies that activate the TSH receptor (TSHR), has only been reported in humans. Thyroiditis-prone NOD.H2h4 mice develop autoantibodies to thyroglobulin and thyroid peroxidase but not to the TSHR. Evidence supports the importance of the shed TSHR A-subunit in the initiation and/or amplification of the autoimmune response to the holoreceptor. Cells expressing the gene for the isolated A-subunit secrete A-subunit protein, a surrogate for holoreceptor A-subunit shedding. NOD.H2h4 mice with the human TSHR A-subunit targeted to the thyroid (a 'self' antigen in such transgenic animals), unlike their wild-type siblings, spontaneously develop pathogenic TSHR antibodies to the human-TSH holoreceptor. These autoantibodies do not recognize the endogenous mouse-TSH holoreceptor and do not cause hyperthyroidism.
METHODS: We have now generated NOD.H2h4 mice with the mouse-TSHR A-subunit transgene targeted to the thyroid. Transgenic mice and wild type littermates were compared for intrathyroidal expression of the mouse A-subunit. Sera from six month old mice were tested for the presence of autoantibodies to thyroglobulin and thyroid peroxidase as well as for pathogenic TSHR antibodies (TSH binding inhibition, bioassay for thyroid stimulating antibodies) and nonpathogenic TSHR antibodies (ELISA).
RESULTS: Expression of the mouse TSHR A-subunit transgene in the thyroid was confirmed by real-time polymerase chain reaction in the transgenics and had no effect on the spontaneous development of autoantibodies to thyroglobulin or thyroid peroxidase. However, unlike the same NOD.H2h4 strain with the human-TSHR A-subunit target to the thyroid, mice expressing intra-thyroidal mouse-TSHR A subunit failed to develop either pathogenic or non-pathogenic TSHR antibodies. The mouse TSHR A-subunit differs from the human TSHR A-subunit in terms of its amino acid sequence and has one less glycosylation site than the human TSHR A-subunit.
CONCLUSIONS: Multiple genetic and environmental factors contribute to the pathogenesis of Graves' disease. The present study suggests that the TSHR A-subunit structure (possibly including post-translational modification such as glycosylation) may explain, in part, why Graves' disease only develops in humans.
METHODS: We have now generated NOD.H2h4 mice with the mouse-TSHR A-subunit transgene targeted to the thyroid. Transgenic mice and wild type littermates were compared for intrathyroidal expression of the mouse A-subunit. Sera from six month old mice were tested for the presence of autoantibodies to thyroglobulin and thyroid peroxidase as well as for pathogenic TSHR antibodies (TSH binding inhibition, bioassay for thyroid stimulating antibodies) and nonpathogenic TSHR antibodies (ELISA).
RESULTS: Expression of the mouse TSHR A-subunit transgene in the thyroid was confirmed by real-time polymerase chain reaction in the transgenics and had no effect on the spontaneous development of autoantibodies to thyroglobulin or thyroid peroxidase. However, unlike the same NOD.H2h4 strain with the human-TSHR A-subunit target to the thyroid, mice expressing intra-thyroidal mouse-TSHR A subunit failed to develop either pathogenic or non-pathogenic TSHR antibodies. The mouse TSHR A-subunit differs from the human TSHR A-subunit in terms of its amino acid sequence and has one less glycosylation site than the human TSHR A-subunit.
CONCLUSIONS: Multiple genetic and environmental factors contribute to the pathogenesis of Graves' disease. The present study suggests that the TSHR A-subunit structure (possibly including post-translational modification such as glycosylation) may explain, in part, why Graves' disease only develops in humans.
Full text links
Related Resources
Trending Papers
Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.Clinical Research in Cardiology : Official Journal of the German Cardiac Society 2024 April 12
Proximal versus distal diuretics in congestive heart failure.Nephrology, Dialysis, Transplantation 2024 Februrary 30
Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.Mental Health Clinician 2023 October
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.American Journal of Hematology 2024 March 30
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app