Thyroid Hormone Action Indicator Transgenic Mouse: the in vivo model to promote thyroid hormone-related R&D

Obesity and metabolic disorders represent a huge social burden, therefore development of drugs against these problems are of great interest. The very beneficial metabolic effects to decrease body weight and cholesterol levels cannot be exploited in euthyroid patients due to unwanted, e.g. cardiac side effects of thyroid hormone. Thyroid hormone (TH) is a fundamental regulator of metabolism and cell proliferation and its level is subjected to tissue-specific regulation. This development is based on a thyroid hormone-dependent expression of a luciferase reporter protein. THAI represents the first mammalian model for tissue-specific assessment of TH action using an intact machinery of TH metabolism and signalling. THAI mouse also allows the assessment of TH action in live mammals for the first time using in vivo imaging facilitating time series studies and testing of different compounds/doses in the same animal. It was generated using a transposase-mediated approach that allowed the insertion of a single copy of the transgene into the genome that allow quantitative measurements and stable maintenance of the line without segregation of the transgenic cassette.

The attached picture Live imaging of TH action in THAI mouse. In vivo imaging on hypothyroid, euthyroid and T3-treated (1 μg/g bw i.p.) mice followed by i.p. luciferin injection. (arrow on upper panel: brown adipose tissue; circle on lower panel: intestine).

TECHNOLOGY ADVANTAGES:

1. The TH action in the THAI mouse is determined by the fully endogenous set of regulators of thyroid hormone action including thyroid hormone receptors isoforms and their coregulators, the thyroid hormone activating and inactivating deiodinase enzymes and thyroid hormone transporters;
2. It allows the detection of tissue-specific TH action in live animals,
3. It can distinguish between thyroid hormone receptor isoform mediated effects.

THAI has been successfully used

1. to study the cold-induced regulation of TH action in the brown adipose tissue, an important target of obesity research;
2. to test the in vivo efficiency of a thyroid hormone isoform specific compound;
3. to study tissue hypothyroidism and
4. to asses thyroid hormone action in microdissected brain samples.

POTENTIAL APPLICATIONS AND POTENTIAL CUSTOMERS:

THAI mouse provides an excellent in vivo model for pharmaceutical companies aim to develop thyromimetic drugs for tissue-specific TH action or companies running exploratory studies for future drug development. Tissue- or TH receptor isoform specificity of new TH agonist/antagonist compounds could be tested with the help of the THAI mouse. These compounds could impact obesity and cholesterol level: that is a significant market.

THE PROPOSED BUSINESS MODEL:

They are primarily interested in the licensing of THAI mouse. They do not exclude the option to start a start-up company, but they would do it only in the presence of significant industrial interest for the invention.