Endocrine Abstracts (2009) 19 P371

Enlargement of the thyroid gland in a heterozygous PBF knock-in transgenic mouse model

M Read1, J Fong1, G Lewy1, V Smith1, A Turnell1, R Watkins1, R Seed1, S Stewart1, A Warfield2, W Leadbeater1, D Kim1, J Watkinson2, J Franklyn1, K Boelaert1 & C McCabe1


1University of Birmingham, Birmingham, West Midlands, UK; 2University Hospital Birmingham NHS Foundation Trust, Birmingham, West Midlands, UK.


PTTG binding factor (PBF) is a poorly characterised 22 kDa protein that is implicated in the aetiology of pituitary and thyroid tumours. Our recent investigations have attempted to discern the function of PBF in vitro. In particular, we reported that PBF can inhibit the activity of the sodium iodide symporter (NIS), which is responsible for iodide uptake into thyroid cells. However, little is known about the precise role of PBF in vivo. We have now generated a murine transgenic model of targeted overexpression of PBF in the thyroid to investigate its function in vivo. Transgenic mice were generated by pronuclear injection of a HA-tagged PBF transgene driven by the bovine thyroglobulin promoter and founders identified by PCR. Western blot analysis of thyroids dissected from heterozygotes demonstrated elevated levels of PBF-HA compared to wild-type (WT) FVB/N mice with no significant expression in other tissues. Immunohistochemical staining using an anti-HA rabbit polyclonal antibody also detected extensive PBF-HA expression in thyroid follicular epithelial cells. A cohort of 18 heterozygous mice was set up with age and sex matched WT mice. The mean weight of thyroids (2.9±0.9 mg, n=14) dissected from 18-week old heterozygotes was significantly greater (P=0.003) than thyroids from WT mice (1.8±0.3 mg, n=9). At >36 weeks of age the mean thyroid weight of heterozygous mice had further increased to 3.3±0.2 mg (n=4). This increase in thyroid weight was unlikely to be related to differences in total body weight as the mean body weight of both male (31.1±1.3 g) and female (25.0±1.5 g) heterozygotes were not significantly different to male (30.6±0.5 g) and female (23.9±1.8 g) WT mice (P=0.42 and 0.26 respectively). Overall, these results demonstrate that targeted overexpression of PBF causes significant enlargement of the thyroid gland in vivo. We are currently evaluating histological sections for the appearance of hyperplastic and neoplastic changes as well as NIS expression and localization.