NRL-PRL 1647-13 transgenic mice have rat lipocalin 2 (Lcn2 or NRL) promoter driving expression of an 8.5 kb fragment, containing the first five exons and flanking regions of the rat prolactin (Prl) gene, with a 1.5kb deletion in intron C. Prl encodes the anterior pituitary hormone prolactin (PRL), a growth regulator for many tissues including the mammary gland. It also acts as a cytokine in immune system function, metabolism, and cell survival. The 3kb NRL promoter is hormonally nonresponsive, enabling the use of these mice to study the interaction of factors contributing to mammary neoplasia independent of hormonal changes in transgene expression. Mice from line 1647-13 (founder line 23) were selected for further study based on the ability to pass the transgene, fertility, and mammary PRL expression. Mice overexpress prolactin in mammary epithelial cells, and low expression is evident in the spleen and uterus, with barely detectable levels in the cecum. Heterozygous nulliparous females descended from this founder line have a 65% incidence of tumors with mean latency of 16.7 months. Transgenic PRL increases proliferation in morphologically normal mammary alveoli and ducts. Mice develop mammary abnormalities, mammary intraepithelial neoplasias, and diverse invasive neoplasms, many of which express estrogen receptor alpha (ER&alpha;+). Expression of the PRL transgene in combination with other mammary oncogenes accelerates tumor formation. Transgenic PRL also enhances ductal elongation in heterozygous male mice, although they do not display mammary lesions. However, bitransgenic NRL-PRL/TGF&alpha; males develop mammary tumors with 100% incidence. The donating investigator did not attempt to establish a homozygous colony and suggests maintaining this line by breeding hemizyous mice to wildtype mice.

NRL-PRL 1647-13 mice express the rat prolactin gene under the control of the rat lipocalin 2 (Lcn2 or NRL) promoter in mammary epithelial cells, similar to human mammary tumor cells. These mice have a 65% incidence of tumors with mean latency of 16.7 months. NRL-PRL 1647-13 mice provide a model of hormonally-dependent breast cancer.