Disruption of Ini1 leads to peri-implantation lethality and tumorigenesis in mice.
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.
Guidi
C J
CJ
Departments of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Sands
A T
AT
Zambrowicz
B P
BP
Turner
T K
TK
Demers
D A
DA
Webster
W
W
Smith
T W
TW
Imbalzano
A N
AN
Jones
S N
SN
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D016147:Genes, Tumor Suppressor; D051379:Mice; D018345:Mice, Knockout; D000071796:SMARCB1 Protein
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513265:Smarcb1 protein, mouse