Gsα Mutations in Hyperfunctioning Thyroid Adenomas

Murakami, Masami; Kamiya, Yûji; Yanagita, Yasuhiro; Mori, Masataka

doi:10.1016/s0188-4409(99)00078-8

Cited by 7 publications

(8 citation statements)

References 51 publications

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“…Signal transduction is cAMPdependent via a G protein-mediated pathway. Hyperfunctioning adenomas in humans were found to be caused by mutations in the G sa gene (11). However, considerable variation in the prevalence of these mutations in humans has been reported (11,15).…”

Section: Discussionmentioning

confidence: 99%

“…The disease could be an animal model to hyperthyroidism in humans caused by thyroid adenomas or multinodular goiter. The pathogenesis of the disease in humans can be related to mutations in genes that encode for the thyrotropin receptor or for the G sa protein (3)(4)(5)(6)(7)(8)(9)(10)(11). In cats, part of the thyrotropin receptor (TSHR gene codons 480-640) has been analyzed for mutations: in this transmembrane part of the receptor no mutations were found in 11 cats with sporadic thyrotoxicosis and 2 cats with familial thyrotoxicosis (12).…”

Section: Introductionmentioning

confidence: 99%

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Feline Thyroid Adenomas are in Part Associated with Mutations in the G_s_α Gene and not with Polymorphisms Found in the Thyrotropin Receptor

Peeters

Timmermans-Sprang

Mol

2002

Thyroid

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The etiopathogenesis of feline thyrotoxicosis is unknown. The transmembrane part (gene codons 480-640) of the thyrotropin receptor (TSHR) gene of hyperthyroid cats has already been investigated for the presence of stimulating mutations. No mutations were found in this part of the TSHR gene. We have investigated the TSHR gene codons 66-530 for gene mutations in 10 hyperthyroid cats and in 1 euthyroid cat. This part of the TSHR gene encodes the transmembrane part as well as most of the extracellular part of the receptor. The G(s alpha) gene of these cats was also sequenced and subjected to mutational analysis. Although our study revealed a polymorphism in the TSHR gene, no association was found with tumor formation. In 4 of 10 cats with hyperthyroidism a G(s alpha) gene mutation was found. This work suggests that mutations in the extracellular or transmembrane part of the TSHR gene are not likely the cause of feline hyperthyroidism. Mutations in the G(s alpha) gene, however, may play a role in the etiopathogenesis of this disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Feline Thyroid Adenomas are in Part Associated with Mutations in the G_s_α Gene and not with Polymorphisms Found in the Thyrotropin Receptor

Peeters

Timmermans-Sprang

Mol

2002

Thyroid

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“…The glutamine residue is thought to be necessary for the hydrolysis of GTP (Coleman et al, 1994). Mutations analogous to the ones we have used have been shown to lower the GTPase activity in many G-protein α-subunit proteins and, thus, prevent turnover to the inactive GDP-bound state (Landis et al, 1989 ;Murakami et al, 1999). The TRP1-deficient T11 monokaryon strain was co-transformed with the mutated gene-expression vectors (Fig.…”

Section: Scgp-a Scgp-b and Scgp-c Genes Into S Communementioning

confidence: 99%

Suppression of fruit-body formation by constitutively active G-protein α-subunits ScGP-A and ScGP-C in the homobasidiomycete Schizophyllum commune The GenBank accession numbers for the sequences reported in this paper are AB066503, AB051903 and AB051904.

et al. 2002

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The heterotrimeric G-protein α-subunit family plays multiple roles in eukaryotic cells, such as the regulation of growth and development, of pathogenicity and of the transmission of pheromone stimulation. In the homobasidiomycete Schizophyllum commune, some genes encoding heterotrimeric G-protein α-subunits (SCGPα1, SCGPα2, ScGP-A, ScGP-B and ScGP-C) have been reported.In this study, constitutively active mutants of ScGP-A, ScGP-B and ScGP-C were generated by site-directed mutagenesis and introduced into the S. commune monokaryon strain to investigate the function of each gene. Northern analysis showed that the mutated genes were strongly expressed when compared with endogenous G-proteins in many clones. Upon macroscopic examination, some transformed clones expressing ScGP-A (Q207R) and ScGP-C (Q204R) mutant genes exhibited a slight suppression of aerial-hyphae formation in the monokaryon strain. In contrast to the slight suppression of aerial-hyphae formation in the monokaryon, most clones expressing mutated ScGP-A or ScGP-C genes failed to form fruit-bodies in the dikaryon strain. This observation indicated that ScGP-A and ScGP-C played a role in suppressing fruit-body formation in the dikaryon. Furthermore, these phenotypes were similar to the phenotype of the thn mutant in S. commune to some extent. Since the thn-1 gene encodes a putative regulator of the G-protein signalling protein (RGS), ScGP-A and ScGP-C might be targets of thn-1.

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“…Activating mutations may occur in exons 1-9 in these cats; however, there have been very few mutations detected in the extracellular region of the human TSHR gene (Duprez et al 1997b, Kopp et al 1997b, Parma et al 1997, Gruters et al 1998, Biebermann et al 2000. Mutations may also occur in other genes involved in the signalling transduction pathway of the TSHR, and mutations have previously been found in a Gs subunit (a protein coupled to the TSHR) gene, in both human and feline hyperthyroidism (Lyons et al 1990, O'Sullivan et al 1991, Russo et al 1995, Parma et al 1997, Murakami et al 1999, Tonacchera et al 1999, Trulzsch et al 2001, Peeters et al 2002, Vanvooren et al 2002, Georgopoulos et al 2003.…”

Section: Tablementioning

confidence: 99%

Somatic mutations of the thyroid-stimulating hormone receptor gene in feline hyperthyroidism: parallels with human hyperthyroidism

Watson¹,

Radford²,

Kipar³

et al. 2005

Journal of Endocrinology

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Hyperthyroidism is the most common endocrinopathy in cats, and is both clinically and histopathologically very similar to human toxic nodular goitre (TNG). Molecular studies on human TNG have revealed the presence of mis-sense mutations in the thyroid-stimulating hormone receptor (TSHR) gene, most frequently in exon 10. Our hypothesis was that similar mutations exist in hyperthyroid cats. Genomic DNA was extracted from 134 hyperplastic/ adenomatous nodules (from 50 hyperthyroid cats), and analysed for the presence of mutations in exon 10 of the TSHR gene. 11 different mutations were detected, one silent and 10 mis-sense, of which nine were somatic mutations. 28 of the 50 cats (67/134 nodules) had at least one mis-sense mutation. The mis-sense mutations were Met-452

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Gsα Mutations in Hyperfunctioning Thyroid Adenomas

Cited by 7 publications

References 51 publications

Feline Thyroid Adenomas are in Part Associated with Mutations in the G_s_α Gene and not with Polymorphisms Found in the Thyrotropin Receptor

Feline Thyroid Adenomas are in Part Associated with Mutations in the G_s_α Gene and not with Polymorphisms Found in the Thyrotropin Receptor

Suppression of fruit-body formation by constitutively active G-protein α-subunits ScGP-A and ScGP-C in the homobasidiomycete Schizophyllum commune The GenBank accession numbers for the sequences reported in this paper are AB066503, AB051903 and AB051904.

Somatic mutations of the thyroid-stimulating hormone receptor gene in feline hyperthyroidism: parallels with human hyperthyroidism

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Gsα Mutations in Hyperfunctioning Thyroid Adenomas

Cited by 7 publications

References 51 publications

Feline Thyroid Adenomas are in Part Associated with Mutations in the Gsα Gene and not with Polymorphisms Found in the Thyrotropin Receptor

Feline Thyroid Adenomas are in Part Associated with Mutations in the Gsα Gene and not with Polymorphisms Found in the Thyrotropin Receptor

Suppression of fruit-body formation by constitutively active G-protein α-subunits ScGP-A and ScGP-C in the homobasidiomycete Schizophyllum commune The GenBank accession numbers for the sequences reported in this paper are AB066503, AB051903 and AB051904.

Somatic mutations of the thyroid-stimulating hormone receptor gene in feline hyperthyroidism: parallels with human hyperthyroidism

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Resources

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Feline Thyroid Adenomas are in Part Associated with Mutations in the G_s_α Gene and not with Polymorphisms Found in the Thyrotropin Receptor

Feline Thyroid Adenomas are in Part Associated with Mutations in the G_s_α Gene and not with Polymorphisms Found in the Thyrotropin Receptor