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Development of zebrafish medulloblastoma-like PNET model by TALEN-mediated somatic gene inactivation.
Shim, Jaegal; Choi, Jung-Hwa; Park, Moon-Hak; Kim, Hyena; Kim, Jong Hwan; Kim, Seon-Young; Hong, Dongwan; Kim, Sunshin; Lee, Ji Eun; Kim, Cheol-Hee; Lee, Jeong-Soo; Bae, Young-Ki.
Afiliación
  • Shim J; Comparative Biomedicine Research Branch, Research Institute, National Cancer Center, Goyang, Republic of Korea.
  • Choi JH; Department of Biology, Chungnam National University, Daejeon, Republic of Korea.
  • Park MH; Tumor Microenviroment Research Branch, Research Institute, National Cancer Center, Goyang, Republic of Korea.
  • Kim H; Tumor Microenviroment Research Branch, Research Institute, National Cancer Center, Goyang, Republic of Korea.
  • Kim JH; Genome Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
  • Kim SY; Genome Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
  • Hong D; Clinical Genomic Analysis Branch, Research Institute, National Cancer Center, Goyang, Republic of Korea.
  • Kim S; Precision Medicine Branch, Research Institute, National Cancer Center, Goyang, Republic of Korea.
  • Lee JE; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Gangnam-gu, Seoul, Republic of Korea.
  • Kim CH; Department of Biology, Chungnam National University, Daejeon, Republic of Korea.
  • Lee JS; Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
  • Bae YK; Convergence Research Center for Dementia DTC, Korea Institute of Science and Technology, Seoul, Republic of Korea.
Oncotarget ; 8(33): 55280-55297, 2017 Aug 15.
Article en En | MEDLINE | ID: mdl-28903419
Genetically engineered animal tumor models have traditionally been generated by the gain of single or multiple oncogenes or the loss of tumor suppressor genes; however, the development of live animal models has been difficult given that cancer phenotypes are generally induced by somatic mutation rather than by germline genetic inactivation. In this study, we developed somatically mutated tumor models using TALEN-mediated somatic gene inactivation of cdkn2a/b or rb1 tumor suppressor genes in zebrafish. One-cell stage injection of cdkn2a/b-TALEN mRNA resulted in malignant peripheral nerve sheath tumors with high frequency (about 39%) and early onset (about 35 weeks of age) in F0 tp53e7/e7 mutant zebrafish. Injection of rb1-TALEN mRNA also led to the formation of brain tumors at high frequency (58%, 31 weeks of age) in F0 tp53e7/e7 mutant zebrafish. Analysis of each tumor induced by somatic inactivation showed that the targeted genes had bi-allelic mutations. Tumors induced by rb1 somatic inactivation were characterized as medulloblastoma-like primitive neuroectodermal tumors based on incidence location, histopathological features, and immunohistochemical tests. In addition, 3' mRNA Quanti-Seq analysis showed differential activation of genes involved in cell cycle, DNA replication, and protein synthesis; especially, genes involved in neuronal development were up-regulated.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Oncotarget Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Oncotarget Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos