A mouse model with tamoxifen-inducible thyrocyte-specific cre recombinase activity

• Published in: Genesis (New York, N.Y. : 2000) N.Y. : 2000), 2014-04, Vol.52 (4), p.333-340
• Main Authors: Undeutsch, Henriette, Löf, Christoffer, Offermanns, Stefan, Kero, Jukka
• Format: Article
• Language: English
• Subjects: Animals; conditional mutagenesis; Cre recombinase; Cre/loxP-System; Female; Integrases - biosynthesis; Integrases - genetics; Male; Mice, Inbred C57BL; Mice, Transgenic; Organ Specificity; Promoter Regions, Genetic; Recombination, Genetic; tamoxifen; Tamoxifen - pharmacology; thyroglobulin; Thyroglobulin - genetics; thyroid gland; Thyroid Gland - cytology; Thyroid Gland - metabolism; Transcriptional Activation - drug effects
• ISSN: 1526-954X; 1526-968X
• DOI: 10.1002/dvg.22740

Summary We have created a mouse model expressing tamoxifen‐inducible Cre recombinase (CreERT2) under the control of the thyroglobulin (Tg) gene promoter to be able to study the role of defined genetic modifications in the regulation of thyroid function. We chose the thyroglobulin promoter, as it is expressed specifically in the thyroid. In order to obtain reliable expression under the control of the Tg promoter, we used a P1 artificial chromosome (PAC) containing a large piece of the Tg promoter. A tamoxifen inducible CreERT2 construct was selected to avoid the possible consequences of the gene deletion for the development of the thyroid gland, and to study the role of gene deletion in the adult thyroid. Transgenic lines (TgCreERT2) carrying this construct were generated and analyzed by crossing the TgCreERT2 mice with the ROSA26LacZ reporter strain. The activity and specificity of the Cre recombinase was tested by staining for β‐galactosidase activity and by immunohistochemistry using an anti‐Cre‐antibody. In the TgCreERT2xROSA26LacZ reporter line, Cre‐mediated recombination occurred specifically in the thyrocytes only after tamoxifen administration, and no significant staining was observed in controls. The recombination efficiency was nearly complete, since almost all thyrocytes showed X‐gal staining. We could also induce the recombination in utero by giving tamoxifen to the pregnant female. In addition, mice expressing TgCreERT2 had no obvious histological changes, hormonal alterations, or different response to growth stimuli as compared to controls. These results demonstrate that the TgCreERT2 mouse line is a powerful tool to study temporally controlled deletion of floxed genes in the thyroid. genesis 52:333–340, 2014. © 2014 Wiley Periodicals, Inc.