Dicer1 Plays an Important Role in Goiter Development in Mice

Presentation Number: OR44-6
Date of Presentation: June 24th, 2014

Henriette Undeutsch*1, Christoffer Löf2, Matti Poutanen3 and Jukka Kero4
1Univ of Turku, Turku, Finland, 2Univ. of turku, 3University of Turku, Turku, Finland, 4Univ. of Turku, Turku, Finland

Abstract

MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression. Tissue-specific silencing of Dicer1, a key enzyme functioning the microRNA processing, provides a tool to study the influence of RNA interference in the tissue development and function. So far, little is known about miRNA in the development, growth and function of the thyroid gland, but miRNA are described to play an oncogenic role thyroid tumor development.

To understand the role of Dicer1 in thyroid in vivo, we have generated a constitutive, thyrocyte-specific Dicer1 knockout mouse line (cTgKO) by crossing Dicer1 fl/fl mice with Tg-Cre mice expressing the Cre recombinase under the thyroglobulin promoter. To be able to study the role of Dicer1 in adult thyroid we have created an inducible thyrocyte-specific Dicer1 KO model (iTgKO) by using a mouse line expressing a tamoxifen-inducible Cre under the thyroglobulin promoter.
Both mouse lines are lacking Dicer1 in thyrocytes. As a consequence, cTgKO mice showed an altered histology of the thyroid gland with disorganized follicles. Similar histological changes were observed in iTgKO mice 4 weeks after the tamoxifen induction. Furthermore, the cTgKO mice developed mild hypothyroidism with increased serum thyroid stimulating hormone (TSH) bioactivity and decreased free thyroxine (fT4) serum levels compared to the wild-type mice. Interestingly, neither cTgKO nor iTgKO mice respond to goiter-inducing drug treatment. While the control mice showed a 4-fold increased weight of the thyroid gland, there was no significant change in thyroid size or weight of cTgKO and iTgKO mice after.

In summary, these data indicate that Dicer1 plays a crucial role in thyroid function and goiter development. Further characterization and comparison of the constitutive and inducible Tg-Cre Dicer1 KO mice will provide novel information about the role of Dicer1 in the development, function and growth of the thyroid gland.

 

Nothing to Disclose: HU, CL, MP, JK