Disruption of Ini1 leads to peri-implantation lethality and tumorigenesis in mice

SNF5/lNI1 is a component of the ATP-dependent chromatin remodeling enzyme f amily SWI/SNF. Germ line mutations of INI1 have been identified in children with brain and renal rhabdoid tumors, indicating that INI1 is a tumor supp ressor, Here we report that disruption of Ini1 expression in mice results i n early embryonic lethality, Ini1-null embryos die between 3.5 and 5.5 days postcoitum, and Ini1-null blastocysts fail to hatch, form the trophectoder m, or expand the inner cell mass when cultured in vitro. Furthermore, we re port that approximately 15% of Ini1-heterozygous mice present with tumors, mostly undifferentiated or poorly differentiated sarcomas, Tumor formation is associated with a loss of heterozygocity at the Ini1 locus, characterizi ng Ini1 as a tumor suppressor in mice, Thus, Ini1 is essential for embryo v iability and for repression of onco-genesis in the adult organism.