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Open Access Technical advance

Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice

Agnieszka M Zagozdzon1, Patrick O’Leary1, John J Callanan2, John Crown3, William M Gallagher1* and Radoslaw Zagozdzon1

Author Affiliations

1 Cancer Biology and Therapeutics Group, UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland

2 UCD School of Veterinary Medicine & Conway Institute, Belfield, Dublin 4, Ireland

3 Molecular Therapeutics for Cancer Ireland (MTCI), c/o National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland

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BMC Cancer 2012, 12:209  doi:10.1186/1471-2407-12-209

Published: 30 May 2012

Abstract

Background

Numerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study.

Results

A new mouse strain (MMTV-Luc2 mice) expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based in vivo imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled ex vivo at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal.

Conclusions

We have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques.

Keywords:
Transgenic mice; MMTV promoter; Luciferase; Bioluminescence; Breast cancer; in vivo imaging