Abnormal mammary gland development in MMTV-CBLC transgenic mouse.

The CBL family of E3 ubiquitin ligases regulates cell signaling in a number of tissues by promoting degradation of tyrosine kinase receptors such as epidermal growth factor receptor. CBLC, the third member of the CBL family, is expressed in epithelial tissues, including the mammary gland. A transgenic mouse strain expressing a tetracyclin-inducible CBLC in the mammary gland was derived. It was found that CBLC transgene expression reduces the number and length of ducts during the development of the gland. In vivo results support the concept of CBLs as negative regulators of cell proliferation. Alternatively, the phenotype may be due to increased apoptosis. This mouse model may be used to further study regulatory components of the CBL pathway and may be crossed with mice susceptible to develop mammary tumors.