{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:25:39Z","timestamp":1784287539592,"version":"3.55.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,8,18]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>cog\/cog<\/jats:italic>\n                    mice, although the precise molecular defect has remained undefined. Here, we have isolated and cloned a full-length 8.5-kb Tg cDNA from\n                    <jats:italic>cog\/cog<\/jats:italic>\n                    mice and unaffected isogenic AKR\/J mice. Comparison of the complete sequences reveals that\n                    <jats:italic>cog\/cog<\/jats:italic>\n                    mice express a Leu-2263 \u2192 Pro missense mutation in the acetylcholinesterase-homology domain of Tg. Heterologous expression studies in COS cells indicate that\n                    <jats:italic>cog<\/jats:italic>\n                    Tg exhibits a severe defect in exit from the ER. Site-directed mutagenesis of\n                    <jats:italic>cog<\/jats:italic>\n                    Tg to convert the single amino acid back to Leu-2263 restores normal Tg secretion. We conclude that the\n                    <jats:italic>cog<\/jats:italic>\n                    mutation in Tg is responsible for this ER storage disease that causes thyroid dyshormonogenesis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.17.9909","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:39:15Z","timestamp":1027679955000},"page":"9909-9913","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":96,"title":["A single amino acid change in the acetylcholinesterase-like domain of thyroglobulin causes congenital goiter with hypothyroidism in the\n                    <i>cog\/cog<\/i>\n                    mouse: A model of human endoplasmic reticulum storage diseases"],"prefix":"10.1073","volume":"95","author":[{"given":"Paul S.","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism, University of Cincinnati School of Medicine, Cincinnati, OH 45267; Division of Endocrinology and Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461; and Division of Cardiology, Beth Israel Hospital, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaikh Abu","family":"Hossain","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, University of Cincinnati School of Medicine, Cincinnati, OH 45267; Division of Endocrinology and Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461; and Division of Cardiology, Beth Israel Hospital, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Nam","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, University of Cincinnati School of Medicine, Cincinnati, OH 45267; Division of Endocrinology and Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461; and Division of Cardiology, Beth Israel Hospital, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ike","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, University of Cincinnati School of Medicine, Cincinnati, OH 45267; Division of Endocrinology and Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461; and Division of Cardiology, Beth Israel Hospital, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Eun","family":"Yoo","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, University of Cincinnati School of Medicine, Cincinnati, OH 45267; Division of Endocrinology and Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461; and Division of Cardiology, Beth Israel Hospital, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Arvan","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, University of Cincinnati School of Medicine, Cincinnati, OH 45267; 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