Establishment and characterization of MRT cell lines from genetically engineered mouse models and the influence of genetic background on their development |
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| Authors: | Yasumichi Kuwahara E. Lorena Mora‐Blanco Fatima Banine Arlin B. Rogers Christopher Fletcher Larry S. Sherman Charles W. M. Roberts Bernard E. Weissman |
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| Affiliation: | 1. UNC‐Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC;2. Department of Pediatric Oncology, Dana‐Farber Cancer Institute, Children's Hospital Boston and Harvard University, Boston, MA;3. Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR;4. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC;5. Department of Pathology, Brigham and Women's Hospital, Boston, MA;6. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NCTel: +919‐966‐7533, Fax: +919‐966‐9673 |
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| 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 TgT121 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 TgT121;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. |
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| Keywords: | pediatric cancers SWI/SNF complex mouse models of cancer SNF5/INI1 |
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