In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse

Endocrine disruptors are increasingly present pollutants and they can greatly interfere with thyroid hormone economy. This is a major concern since thyroid hormones are important regulators of biological function. One of our major aims is to measure whether specific molecules and their metabolites are able to disrupt thyroid hormone economy in vivo in mammals.

While there are screening methods for such compounds, little is known on how they act in vivo on tissues. This is due to the lack of proper test systems aiming to characterize their tissue specific effects. Additionally, this would require the quantitative measurement of local thyroid hormone action that is also challenging.

We developed the thyroid hormone action indicator, or THAI mouse model, in order to characterize thyroid hormone action in the tissues. We realized this would be adequate to measure the thyroid related effects of endocrine disruptors in a tissue specific manner. Notably, the THAI model would allow us to do so in a living mammalian organism.

The THAI model enables the in vivo detection of endogenous changes in local thyroid hormone action through bioluminescent imaging. This enables the use of crossover designs, follow up studies, self-control studies, and continuous disruptor exposure. Notably, the THAI model enables us to lower the required number of animals used in the study.