Genetically modified mouse models to investigate thyroid development, function and growth

Molecular defects in thyroid dysgenesis

“…Abbreviations: E, embryonic day; TSHR, thyroid‐stimulating hormone receptor. Adapted from References [Colour figure can be viewed at wileyonlinelibrary.com]…”

“…Abbreviations: E, embryonic day; TSHR, thyroidstimulating hormone receptor. Adapted from References 20,71,72 regulated by NKX2-1, suggesting that any alteration in this loop could predispose to TD. 70 Finally, as demonstrated by using multitarget-knockout mice, TD can rise as a polygenic disease.…”

Experimental Modeling Of Hypothyroidism: Principles, Methods, Several Advanced Research Directions In Cardiology

“…In general, the hypothyroidism modeling principles are based on the creation of the above-described conditions for hypothyroidism development in laboratory animals, namely, the use of food with a limited iodine content (dietary models) [17][18][19], removal of all or part of the thyroid gland (thyroidectomy) [12,20], or thyroid blood supply disturbance due to ligation/coagulation of the superior and inferior thyroid arteries feeding it [21] (surgical models), administration of antithyroid (thyreostatic) drugs in the animal body [15,22,23] (medicamentous models), mammalian genome editing using molecular genetic methods (genetic models) [24][25][26], exposure of an animal body to a certain dose of a radioactive iodine (radioactive models) [27,28], and administration of an immunosuppressive agent in an animal body (immunological model) [29]. These modeling principles allow to simulate almost all the basic conditions for hypothyroidism development necessary for the specific goals and objectives of the study.…”

Mechanisms of thyrotropin receptor–mediated phenotype variability deciphered by gene mutations and M453T-knockin model

“…Furthermore, our previous findings confirm the primary roles of Gα s -and Gα q/11 -mediated signaling in the thyrocytes, as we have used different mouse models to investigate the role of G protein signaling in the pathogenesis of TSHR-mediated disease. In these models, we tested the effect of thyrocyte-specific G protein deficiencies on thyroid function and growth (21)(22)(23), and we observed that only thyrocyte-specific Gα s -deficient mice developed acute hypothyroidism (22). While mice lacking Gα q/11 -mediated signaling in the thyroid had impaired thyroid growth but developed subclinical to overt hypothyroidism only at older ages (7), the conditional Gα 12/13 -deficient mice had no obvious phenotypes (21).…”

“…In these models, we tested the effect of thyrocyte-specific G protein deficiencies on thyroid function and growth (21)(22)(23), and we observed that only thyrocyte-specific Gα s -deficient mice developed acute hypothyroidism (22). While mice lacking Gα q/11 -mediated signaling in the thyroid had impaired thyroid growth but developed subclinical to overt hypothyroidism only at older ages (7), the conditional Gα 12/13 -deficient mice had no obvious phenotypes (21). Surprisingly, strong constitutive activity of both Gα s and Gα q/11 , detected in our recently developed NAH mouse model (23), carrying a patient-derived TSHR D633H mutation (24) led to only relatively mild and transient hyperthyroidism but advanced to papillary thyroid carcinoma (PTC).…”