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Rapid Generation of Somatic Mouse Mosaics with Locus-Specific, Stably Integrated Transgenic Elements.
Kim, Gi Bum; Rincon Fernandez Pacheco, David; Saxon, David; Yang, Amy; Sabet, Sara; Dutra-Clarke, Marina; Levy, Rachelle; Watkins, Ashley; Park, Hannah; Abbasi Akhtar, Aslam; Linesch, Paul W; Kobritz, Naomi; Chandra, Swasty S; Grausam, Katie; Ayala-Sarmiento, Alberto; Molina, Jessica; Sedivakova, Kristyna; Hoang, Kendy; Tsyporin, Jeremiah; Gareau, Daniel S; Filbin, Mariella G; Bannykh, Serguei; Santiskulvong, Chintda; Wang, Yizhou; Tang, Jie; Suva, Mario L; Chen, Bin; Danielpour, Moise; Breunig, Joshua J.
Afiliação
  • Kim GB; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Rincon Fernandez Pacheco D; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Saxon D; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Yang A; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Sabet S; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Dutra-Clarke M; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Levy R; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Watkins A; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Park H; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Abbasi Akhtar A; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Linesch PW; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Kobritz N; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Chandra SS; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Grausam K; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Ayala-Sarmiento A; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Molina J; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Sedivakova K; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Hoang K; Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, 1156 High St., Santa Cruz, CA 95064, USA.
  • Tsyporin J; Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, 1156 High St., Santa Cruz, CA 95064, USA.
  • Gareau DS; Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY 10065, USA.
  • Filbin MG; Department of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Bannykh S; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Santiskulvong C; Center for Neural Sciences in Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Wang Y; Center for Neural Sciences in Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Tang J; Center for Neural Sciences in Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Suva ML; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Chen B; Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, 1156 High St., Santa Cruz, CA 95064, USA.
  • Danielpour M; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Breunig JJ; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Center for Neural Sciences in Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Sa
Cell ; 179(1): 251-267.e24, 2019 09 19.
Article em En | MEDLINE | ID: mdl-31539496
ABSTRACT
In situ transgenesis methods such as viruses and electroporation can rapidly create somatic transgenic mice but lack control over copy number, zygosity, and locus specificity. Here we establish mosaic analysis by dual recombinase-mediated cassette exchange (MADR), which permits stable labeling of mutant cells expressing transgenic elements from precisely defined chromosomal loci. We provide a toolkit of MADR elements for combination labeling, inducible and reversible transgene manipulation, VCre recombinase expression, and transgenesis of human cells. Further, we demonstrate the versatility of MADR by creating glioma models with mixed reporter-identified zygosity or with "personalized" driver mutations from pediatric glioma. MADR is extensible to thousands of existing mouse lines, providing a flexible platform to democratize the generation of somatic mosaic mice. VIDEO ABSTRACT.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Mutagênese Insercional / Marcação de Genes / Transgenes / Modelos Animais de Doenças / Loci Gênicos / Glioma Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Mutagênese Insercional / Marcação de Genes / Transgenes / Modelos Animais de Doenças / Loci Gênicos / Glioma Idioma: En Ano de publicação: 2019 Tipo de documento: Article