title: Establishment of an Effective Radioiodide Thyroid Ablation Protocol in Mice.
abstract: Due to the high variance in available protocols on iodide-131 ((131)I) ablation in rodents, we set out to establish an effective method to generate a thyroid-ablated mouse model that allows the application of the sodium iodide symporter (NIS) as a reporter gene without interference with thyroidal NIS. We tested a range of (131)I doses with and without prestimulation of thyroidal radioiodide uptake by a low-iodine diet and thyroid-stimulating hormone (TSH) application. Efficacy of induction of hypothyroidism was tested by measurement of serum T4 concentrations, pituitary TSHβ and liver deiodinase type 1 (DIO1) mRNA expression, body weight analysis, and (99m)Tc-pertechnetate scintigraphy. While 200 µCi (7.4 MBq) (131)I alone was not sufficient to abolish thyroidal T4 production, 500 µCi (18.5 MBq) (131)I combined with 1 week of a low-iodine diet decreased serum concentrations below the detection limit. However, the high (131)I dose resulted in severe side effects. A combination of 1 week of a low-iodine diet followed by injection of bovine TSH before the application of 150 µCi (5.5 MBq) (131)I decreased serum T4 concentrations below the detection limit and significantly increased pituitary TSHβ concentrations. The systemic effects of induced hypothyroidism were shown by growth arrest and a decrease in liver DIO1 expression below the detection limit. (99m)Tc-pertechnetate scintigraphy revealed absence of thyroidal (99m)Tc-pertechnetate uptake in ablated mice. In summary, we report a revised protocol for radioiodide ablation of the thyroid gland in the mouse to generate an in vivo model that allows the study of thyroid hormone action using NIS as a reporter gene.
authors.affiliation: Department of Internal Medicine II, Munich, Germany.
authors.forename: Kathrin A
authors.initials: KA
authors.lastname: Schmohl
authors.affiliation: Department of Internal Medicine II, Munich, Germany.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Müller
authors.affiliation: Department of Internal Medicine II, Munich, Germany.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schwenk
authors.affiliation: Department of Internal Medicine II, Munich, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Knoop
authors.affiliation: Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Eddy
authors.initials: E
authors.lastname: Rijntjes
authors.affiliation: Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
authors.affiliation: Leibniz Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Heuer
authors.affiliation: Department of Nuclear Medicine, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.affiliation: Department of Internal Medicine II, Munich, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Göke
authors.affiliation: Medical Policlinic IV, University Hospital of Munich, Munich, Germany.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Nelson
authors.affiliation: Department of Internal Medicine II, Munich, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Spitzweg
keywords: Hypothyroidism; Mouse model; Radioiodide; Thyroid ablation