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Establishment and characterization of MRT cell lines from genetically engineered mouse models and the influence of genetic background on their development
Author(s) -
Kuwahara Yasumichi,
MoraBlanco E. Lorena,
Banine Fatima,
Rogers Arlin B.,
Fletcher Christopher,
Sherman Larry S.,
Roberts Charles W. M.,
Weissman Bernard E.
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27976
Subject(s) - penetrance , transgene , biology , allele , cancer research , genetically modified mouse , gene , genetics , phenotype
Abstract Malignant rhabdoid tumors (MRTs) are rare, aggressive cancers occuring in young children primarily through inactivation of the SNF5(INI1, SMARCB1 ) tumor suppressor gene. We and others have demonstrated that mice heterozygous for a Snf5 null allele develop MRTs with partial penetrance. We have also shown that Snf5 +/− mice that lack expression of the pRb family, due to TgT 121 transgene expression, develop MRTs with increased penetrance and decreased latency. Here, we report that altering the genetic background has substantial effects upon MRT development in Snf5 +/−‐ and TgT 121 ; Snf5 +/− mice, with a mixed F1 background resulting in increased latency and the appearance of brain tumors. We also report the establishment of the first mouse MRT cell lines that recapitulate many features of their human counterparts. Our studies provide further insight into the genetic influences on MRT development as well as provide valuable new cell culture and genetically engineered mouse models for the study of CNS‐MRT etiology.