Uterine-Specific Knockout of Tsc-2: A Mouse Model for Lymphangioleiomyomatosis.

摘要

Our goal was to develop and characterize a mouse model for the disease lymphangioleiomyomatosis (LAM). This disease is found almost exclusively in women and is due to a mutation in one of the two TSC suppressor genes. Women with LAM develop smooth muscle-like tumors in the lungs that grow progressively, often leading to lung failure. Evidence suggested that these tumors do not originate in the lungs but instead are metastatic from another location in the body. Our hypothesis was that lung LAM tumors were actually metastatic from smooth muscle myometrial cells in the uterus, thus explaining both the appearance of the LAM cells as well as the overwhelming female prevalence. Thus, we created a uterine-specific TSC-2 knockout mouse. These mice developed uterine tumors that were completely dependent on estrogen for growth. Importantly, as mice aged above 30 weeks, 75% of them developed myometrial lung tumors that shared many features consistent with LAM. These data were just published in and featured on the cover of the September, 2013 issue of Molecular Endocrinology. This is an exciting new model, and we hope to use it to both better understand LAM and to help test novel treatment options for LAM.