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Updated: May 2, 2026

Generation of a Mouse Spontaneous Autoimmune Thyroiditis Model
Published on: March 17, 2023
A Japanese family with nonautoimmune hyperthyroidism caused by a novel heterozygous thyrotropin receptor gene
Akie Nakamura1, Shuntaro Morikawa1, Hayato Aoyagi2
1Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan.
Background:
Hyperthyroidism caused by activating mutations of the thyrotropin receptor gene (TSHR) is rare in the pediatric population.
Methods:
We found a Japanese family with hyperthyroidism without autoantibody. DNA sequence analysis of TSHR was undertaken in this family. The functional consequences for the Gs-adenylyl cyclase and Gq/11-phospholipase C signaling pathways and cell surface expression of receptors were determined in vitro using transiently transfected human embryonic kidney 293 cells.
Results:
We identified a heterozygous mutation (M453R) in exon 10 of TSHR. In this family, this mutation was found in all individuals who exhibited hyperthyroidism. The results showed that this mutation resulted in constitutive activation of the Gs-adenylyl cyclase system. However, this mutation also caused a reduction in the activation capacity of the Gq/11-phospholipase C pathway, compared with the wild type.
Conclusion:
We demonstrate that the M453R mutation is the cause of nonautoimmune hyperthyroidism.
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