Epithelial Transplantation into the Cleared Mammary Fat Pad

Established decades ago by DeOme and coworkers, transplantation of mammary epithelial cells or fragments into the “cleared” mammary fat pad of a host mouse continues to be an essential technique in the study of mammary gland biology. The technique exploits the fact that the murine mammary epithelium undergoes most of its development after puberty. Taking advantage of this early developmental stage, the inguinal mammary fat pad of a prepubertal host mouse is “cleared” of its rudimentary epithelium by surgically removing the fat pad tissue between the nipple and lymph node. The surgical resection leaves an epithelium-free fat pad that can be repopulated with transplanted mammary epithelial cells or tissue fragments from an exogenous source. With this technique, the natural development of the epithelial transplant can be studied during puberty, progressive stages of pregnancy and lactation, or in response to exogenous hormones. When applied to gene-knockout mouse models, the technique has proven to be indispensable for bypassing both embryonic lethal phenotypes and reproductive defects that would ordinarily preclude the study of such genotypes in the mammary epithelium of the adult or pregnant mouse. Beyond addressing the direct role of a gene product in the mammary epithelium, this technique is frequently used to assess the relative regenerative potential of epithelial cell populations that are enriched for (or depleted of) mammary stem or progenitor cells.