Histone demethylase JARID1B (Kdm5b, lysine (K)-specific demethylase 5B) promotes luminal lineage transcription programs in the mammary gland and fine-tunes systemic estrogen levels. It is overexpressed in HER2+ breast cancer and many breast cancer cell lines, making it a potential target for treatment.
These mice carry a β-geo genetrap/knockout mutation located in intron 2 of the mouse Kdm5b gene that creates a premature termination of the protein before the AT-rich interactive domain (ARID). Western blot analysis using an antibody against the C terminus shows that full-length protein is undetectable. β-geo can be used effectively for lacZ staining of cells normally expressing JARID1B.
Unlike other knockouts of this gene, the majority of homozygotes from this line are viable beyond embryonic and neonatal stages. Some animals die between 3-6 months of age for undetermined reasons. Others can live up to 2 years. Mice exhibit decreased body weight, premature mortality, decreased female fertility, lower uterine weight, and delayed mammary gland development. Serum estrogen levels are decreased and reduced mammary epithelial cell proliferation in observed in early puberty.
Ex vivo cells derived from the mammary glands of homozygotes exhibit diminished expression of key regulators of mammary gland morphogenesis and luminal lineage specification along with increased expression of a mammary stem cell signature.
