Abstract
The FVB/N mouse strain is extensively used in the development of animal models for breast cancer research. Recently it has been reported that the aging FVB/N mice develop spontaneous mammary lesions and tumors accompanied with abnormalities in the pituitary glands. These observations have a great impact on the mouse models of human breast cancer. We have developed a population of inbred FVB/N mice (designated FVB/N-RC) that have been genetically isolated for 20 years. To study the effects of age and parity on abnormalities of the mammary glands of FVB/N-RC mice, twenty-five nulliparous and multiparous (3–4 pregnancies) females were euthanized at 16–22 months of age. Examination of the mammary glands did not reveal macroscopic evidence of mammary gland tumors in either aged-nulliparous or multiparous FVB/N-RC mice (0/25). However, histological analysis of the mammary glands showed rare focal nodules of squamous changes in 2 of the aged multiparous mice. Mammary gland hyperplasia was detected in 8% and 71% of the aged-nulliparous and aged-multiparous mice, respectively. Epithelial contents and serum levels of triiodothyronine were significantly higher in the experimental groups than the 14-wk-old control mice. Immuno-histochemical staining of the pituitary gland pars distalis showed no difference in prolactin staining between the control and the aged mice. Tissue transplant and dilution studies showed no effect of age and/or parity on the ability of putative progenitor cells present among the injected mammary cells to repopulate a cleared fat pad and develop a full mammary gland outgrowth. This FVB/N-RC mouse substrain is suitable to develop mouse models for breast cancer.
Highlights
Advances in breast cancer treatment require better understanding of the genetics and biology of the disease
Neither age and/or parity resulted in spontaneous mammary tumor development or affected the ability of the mammary stem cells to repopulate the mammary gland; we propose the FVB/N-RC mouse substrain as a suitable model for the development of mammary gland tumor models
While 35% of the aged-nulliparous mammary glands showed few budding alveoli originating from the primary duct (Fig. 1A, panels b and c), 93% of the agedmultiparous females showed higher levels of alveolar content (Fig. 1A, panels e and f)
Summary
Advances in breast cancer treatment require better understanding of the genetics and biology of the disease This requires the development of better in vitro and in vivo models of human breast cancer. Transgenic/knock-in and knockout mouse models have been used widely to observe in vivo the role of genes in initiation and progression of the disease. Their use has dramatically increased during the past decade. The FVB strain of mice is widely used for the generation of models of human breast cancer. Human embryonal carcinoma cells have been reprogrammed to human mammary cells in the mouse in vivo [4]
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