Department of Pathology; Department of Cell Biology
Medical Subject Headings
Animals; Cell Transformation, Neoplastic; Chromosomal Proteins, Non-Histone; DNA-Binding Proteins; Embryonic and Fetal Development; *Gene Expression Regulation, Developmental; Genes, Tumor Suppressor; Mice; Mice, Knockout
Cell Biology | Life Sciences | Medicine and Health Sciences
SNF5/INI1 is a component of the ATP-dependent chromatin remodeling enzyme family SWI/SNF. Germ line mutations of INI1 have been identified in children with brain and renal rhabdoid tumors, indicating that INI1 is a tumor suppressor. Here we report that disruption of Ini1 expression in mice results in early embryonic lethality. Ini1-null embryos die between 3.5 and 5.5 days postcoitum, and Ini1-null blastocysts fail to hatch, form the trophectoderm, or expand the inner cell mass when cultured in vitro. Furthermore, we report 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, characterizing Ini1 as a tumor suppressor in mice. Thus, Ini1 is essential for embryo viability and for repression of oncogenesis in the adult organism.
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Citation: Mol Cell Biol. 2001 May;21(10):3598-603. Link to article on publisher's site