{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T04:16:23Z","timestamp":1778991383867,"version":"3.51.4"},"reference-count":27,"publisher":"The Endocrine Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The Pax8\u2212\/\u2212 mouse provides an ideal animal model to study the consequences of congenital hypothyroidism, because its only known defect is the absence of thyroid follicular cells. Pax8\u2212\/\u2212 mice are, therefore, completely athyroid in postnatal life and die around weaning unless they are substituted with thyroid hormones. As reported recently, Pax8\u2212\/\u2212 mice can also be rescued and survive to adulthood by the additional elimination of the entire thyroid hormone receptor \u03b1 (TR\u03b1) gene, yielding Pax8\u2212\/\u2212TR\u03b1o\/o double-knockout animals. This observation has led to the hypothesis that unliganded TR\u03b11 might be responsible for the lethal phenotype observed in Pax8\u2212\/\u2212 animals. In this study we report the generation of Pax8\u2212\/\u2212TR\u03b11\u2212\/\u2212 double-knockout mice that still express the non-T3-binding TR isoforms \u03b12 and \u0394\u03b12. These animals closely resemble the phenotype of Pax8\u2212\/\u2212 mice, including growth retardation and a completely distorted appearance of the pituitary with thyrotroph hyperplasia and hypertrophy, extremely high TSH mRNA levels, reduced GH mRNA expression, and the almost complete absence of lactotrophs. Like Pax8\u2212\/\u2212 mice, Pax8\u2212\/\u2212TR\u03b11\u2212\/\u2212 compound mutants die around weaning unless they are substituted with thyroid hormones. These findings do not support the previous interpretation that the short life span of Pax8\u2212\/\u2212 mice is due to the negative effects of the TR\u03b11 aporeceptor, but, rather, suggest a more complex mechanism involving TR\u03b12 and an unliganded TR isoform.<\/jats:p>","DOI":"10.1210\/en.2005-0114","type":"journal-article","created":{"date-parts":[[2005,4,1]],"date-time":"2005-04-01T01:34:21Z","timestamp":1112319261000},"page":"3179-3184","source":"Crossref","is-referenced-by-count":29,"title":["Athyroid Pax8\u2212\/\u2212 Mice Cannot Be Rescued by the Inactivation of Thyroid Hormone Receptor \u03b11"],"prefix":"10.1210","volume":"146","author":[{"given":"Jens","family":"Mittag","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So\u0308nke","family":"Friedrichsen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heike","family":"Heuer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silke","family":"Polsfuss","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theo J.","family":"Visser","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Bauer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071612475569000_R1","first-page":"94","article-title":"The role of thyroid hormones in prenatal and neonatal neurological development: current 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