The serine/threonine kinase, Krct, affects endbud morphogenesis during murine mammary gland development

Abstract

STK16/Krct (Kinase related to cerevisiae and thaliana) is a ubiquitously expressed member of a unique family of serine/threonine protein kinases that is conserved among all eukaryotes. Despite its cloning 6 years ago to date, the function of this kinase remains unknown. In an attempt to identify a function for Krct, we have generated a doxycycline-dependent transgenic mouse model that permits the inducible overexpression of Krct in the mammary glands of mice treated with tetracycline derivatives. Analysis of these mice reveals that modest overexpression of Krct in the mammary gland during puberty results in duplication of the terminal endbud axis such that multiple, rather than single, budding structures arise at the ends of primary ducts. Supernumerary endbuds in Krct overexpressing mice resemble wild-type terminal endbuds with regard to cellular proliferation rates and localization of cap cells, myoepithelial cells and body cells. However, aberrant transgenic endbuds are surrounded by an increased amount of periductal stroma that in many cases encompasses the entire endbud. These data suggest that Krct may play a role in regulating stromal-epithelial interactions that occur during ductal morphogenesis in the mammary gland.