ArticleProceedings of the National Academy of Sciences of the United States of America1998
A single amino acid change in the acetylcholinesterase-like domain of thyroglobulin causes congenital goiter with hypothyroidism in the cog/cog mouse: a model of human endoplasmic reticulum storage diseases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 119 citations in OpenAlex.
- Thyroid Hormone Synthesis Without Thyroglobulin.Thyroid : official journal of the American Thyroid Association · 2026Article
- Molecular recognition of thyroglobulin by sortilin.Nature communications · 2026Article
- Public Cohort Analysis Identifies Thyroglobulin Variants as Hypothyroidism Risk Factors.bioRxiv : the preprint server for biology · 2025Article
- Thyroidal expression of ER molecular chaperone GRP170 is required for efficient TSH-mediated thyroid hormone synthesis.JCI insight · 2025Article
- A Genetically-Engineered Thyroid Gland Built for Selective Triiodothyronine Secretion.International journal of molecular sciences · 2025Article
- LINE-1 transposition into murine Thyroglobulin results in congenital thyroid dysplasia.PloS one · 2025Article
- The p.Pro2232Leu variant in the ChEL domain of thyroglobulin gene causes intracellular transport disorder and congenital hypothyroidism.Endocrine · 2023Article
- Defective Thyroglobulin: Cell Biology of Disease.International journal of molecular sciences · 2022Review
- Germline Saturation Mutagenesis Induces Skeletal Phenotypes in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- Thyroid hormone synthesis continues despite biallelic thyroglobulin mutation with cell death.JCI insight · 2021Article
- Cell death-associated lipid droplet protein CIDE-A is a noncanonical marker of endoplasmic reticulum stress.JCI insight · 2021Article
- Thyroglobulin Interactome Profiling Defines Altered Proteostasis Topology Associated With Thyroid Dyshormonogenesis.Molecular & cellular proteomics : MCP · 2021Article
- Asynchrony of Apical Polarization, Luminogenesis, and Functional Differentiation in the Developing Thyroid Gland.Frontiers in endocrinology · 2021Article
- Thyrocyte cell survival and adaptation to chronic endoplasmic reticulum stress due to misfolded thyroglobulin.The Journal of biological chemistry · 2020Article
- Lessons from animal models of endocrine disorders caused by defects of protein folding in the secretory pathway.Molecular and cellular endocrinology · 2020Review
- Preservation of circadian rhythms by the protein folding chaperone, BiP.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- The role of thyroglobulin in thyroid hormonogenesis.Nature reviews. Endocrinology · 2019Review
- Interferon-α Triggers Autoimmune Thyroid Diseases via Lysosomal-Dependent Degradation of Thyroglobulin.The Journal of clinical endocrinology and metabolism · 2018Article
- A novel mutation in the TG gene (G2322S) causing congenital hypothyroidism in a Sudanese family: a case report.BMC medical genetics · 2018Article
- Intracellular retention of thyroglobulin in the absence of the low-density lipoprotein receptor-associated protein (RAP) is likely due to premature binding to megalin in the biosynthetic pathway.Journal of endocrinological investigation · 2016Article
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6 authors at 2 institutions in 1 country.
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Abstract
Newly synthesized thyroglobulin (Tg), the major secretory glycoprotein of the thyroid gland, folds and homodimerizes in the endoplasmic reticulum (ER) before its export to the site of iodination, where it serves as the precursor for thyroid hormone synthesis. In families with defective Tg export, affected individuals suffer from a thyroidal ER storage disease characterized by a distended thyrocyte ER containing misfolded Tg, along with induced ER molecular chaperones. Inherited as an autosomal recessive trait, deficient Tg causes congenital hypothyroidism in newborns that, if untreated, results in goiter along with serious cognitive and growth defects. Recently, a similar phenotype has been observed in inbred cog/cog mice, although the precise molecular defect has remained undefined. Here, we have isolated and cloned a full-length 8.5-kb Tg cDNA from cog/cog mice and unaffected isogenic AKR/J mice. Comparison of the complete sequences reveals that cog/cog mice express a Leu-2263 --> Pro missense mutation in the acetylcholinesterase-homology domain of Tg. Heterologous expression studies in COS cells indicate that cog Tg exhibits a severe defect in exit from the ER. Site-directed mutagenesis of cog Tg to convert the single amino acid back to Leu-2263 restores normal Tg secretion. We conclude that the cog mutation in Tg is responsible for this ER storage disease that causes thyroid dyshormonogenesis.
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