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PMID: 30302402 Published · epublish English Journal Article

Genetically engineered minipigs model the major clinical features of human neurofibromatosis type 1.

Communications biology ·Vol. 1 ·2018-00-00 ·页码 158

Isakson SH, Rizzardi AE, Coutts AW, Carlson DF, Kirstein MN, Fisher J, Vitte J, Williams KB, Pluhar GE, Dahiya S, Widemann BC, Dombi E, Rizvi T, Ratner N, Messiaen L, Stemmer-Rachamimov AO, Fahrenkrug SC, Gutmann DH, Giovannini M, Moertel CL, Largaespada DA, Watson AL

Abstract

Neurofibromatosis Type 1 (NF1) is a genetic disease caused by mutations in Neurofibromin 1 (NF1). NF1 patients present with a variety of clinical manifestations and are predisposed to cancer development. Many NF1 animal models have been developed, yet none display the spectrum of disease seen in patients and the translational impact of these models has been limited. We describe a minipig model that exhibits clinical hallmarks of NF1, including café au lait macules, neurofibromas, and optic pathway glioma. Spontaneous loss of heterozygosity is observed in this model, a phenomenon also described in NF1 patients. Oral administration of a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor suppresses Ras signaling. To our knowledge, this model provides an unprecedented opportunity to study the complex biology and natural history of NF1 and could prove indispensable for development of imaging methods, biomarkers, and evaluation of safety and efficacy of NF1-targeted therapies.

作者与单位
共 22 位作者,点击展开单位 / ORCID
Isakson Sara H
Masonic Cancer Center, University of Minnesota, Room 3-129, Cancer Cardiovascular Research Building, 2231 6th Street SE, Minneapolis, MN, 55455, USA.
Rizzardi Anthony E
Recombinetics Inc., 1246 University Avenue W., Suite 301, St. Paul, MN, 55104, USA.
Coutts Alexander W
Recombinetics Inc., 1246 University Avenue W., Suite 301, St. Paul, MN, 55104, USA.
Carlson Daniel F
Recombinetics Inc., 1246 University Avenue W., Suite 301, St. Paul, MN, 55104, USA.
Kirstein Mark N
Masonic Cancer Center, University of Minnesota, Room 3-129, Cancer Cardiovascular Research Building, 2231 6th Street SE, Minneapolis, MN, 55455, USA. | Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Room 459, 717 Delaware Street SE, Minneapolis, MN, 55414, USA.
Fisher James
Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Room 459, 717 Delaware Street SE, Minneapolis, MN, 55414, USA.
Vitte Jeremie ORCID
Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA and Jonsson Comprehensive Cancer Center (JCCC), University of California Los Angeles, 675 Charles E Young Drive S, MRL Room 2240, Los Angeles, CA, 90095, USA.
Williams Kyle B
Masonic Cancer Center, University of Minnesota, Room 3-129, Cancer Cardiovascular Research Building, 2231 6th Street SE, Minneapolis, MN, 55455, USA.
Pluhar G Elizabeth
Masonic Cancer Center, University of Minnesota, Room 3-129, Cancer Cardiovascular Research Building, 2231 6th Street SE, Minneapolis, MN, 55455, USA. | Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, 1365 Gortner Avenue, St. Paul, MN, 55108, USA.
Dahiya Sonika
Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, 660S. Euclid Avenue, CB 8118, St. Louis, MO, 63110, USA.
Widemann Brigitte C
Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, CRC 1-5750, 10 Center Drive, Bethesda, MD, 20892, USA.
Dombi Eva
Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, CRC 1-5750, 10 Center Drive, Bethesda, MD, 20892, USA.
Rizvi Tilat
Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Cincinnati Children's Hospital, University of Cincinnati, 3333 Burnet Avenue, ML 7013, Cincinnati, OH, 45229, USA.
Ratner Nancy
Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Cincinnati Children's Hospital, University of Cincinnati, 3333 Burnet Avenue, ML 7013, Cincinnati, OH, 45229, USA.
Messiaen Ludwine
Medical Genomics Laboratory, Department of Genetics, University of Alabama at Birmingham, Kaul Building, 720 20th Street South, Birmingham, AL, 35294, USA.
Stemmer-Rachamimov Anat O
Department of Pathology, Massachusetts General Hospital, Warren Building, Room 333A, 55 Fruit Street, Boston, MA, 02114, USA.
Fahrenkrug Scott C
Recombinetics Inc., 1246 University Avenue W., Suite 301, St. Paul, MN, 55104, USA.
Gutmann David H
Department of Neurology, Washington University School of Medicine, Box 8111, 660S. Euclid Avenue, St. Louis, MO, 63110, USA.
Giovannini Marco
Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA and Jonsson Comprehensive Cancer Center (JCCC), University of California Los Angeles, 675 Charles E Young Drive S, MRL Room 2240, Los Angeles, CA, 90095, USA.
Moertel Christopher L
Masonic Cancer Center, University of Minnesota, Room 3-129, Cancer Cardiovascular Research Building, 2231 6th Street SE, Minneapolis, MN, 55455, USA. | Department of Pediatrics, University of Minnesota, Room 3-129, Cancer Cardiovascular Research Building, 2231 6th Street SE, Minneapolis, MN, 55455, USA.
Largaespada David A
Masonic Cancer Center, University of Minnesota, Room 3-129, Cancer Cardiovascular Research Building, 2231 6th Street SE, Minneapolis, MN, 55455, USA. | Department of Pediatrics, University of Minnesota, Room 3-129, Cancer Cardiovascular Research Building, 2231 6th Street SE, Minneapolis, MN, 55455, USA.
Watson Adrienne L
Recombinetics Inc., 1246 University Avenue W., Suite 301, St. Paul, MN, 55104, USA. wats0189@umn.edu.
Article Info
Journal
Communications biology
Abbr.
Commun Biol
ISSN
2399-3642
Corresponding email
Published
2018-00-00
电子出版
2018-00-02
页码
158
Language
English
Country/Region
England
NLM ID
101719179
基金资助
NCI NIH HHS · P30 CA077598 · United States
NCI NIH HHS · P50 CA211015 · United States
NINDS NIH HHS · R01 NS091037 · United States
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