Genetically engineered minipigs model the major clinical features of human neurofibromatosis type 1
| Autor: | Sara H. Isakson, Anat Stemmer-Rachamimov, Christopher L. Moertel, David A. Largaespada, David H. Gutmann, Ludwine Messiaen, Alexander W. Coutts, G. Elizabeth Pluhar, Jeremie Vitte, Adrienne L. Watson, Scott C. Fahrenkrug, Nancy Ratner, Daniel F. Carlson, Marco Giovannini, Anthony E. Rizzardi, Eva Dombi, Mark N. Kirstein, Kyle B. Williams, James Fisher, Tilat A. Rizvi, Sonika Dahiya, Brigitte C. Widemann |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities Medicine (miscellaneous) Disease General Biochemistry Genetics and Molecular Biology Article Neurofibromatosis Loss of heterozygosity 03 medical and health sciences 0302 clinical medicine Rare Diseases Medicine Protein kinase A neoplasms lcsh:QH301-705.5 Cancer biology business.industry Genetically engineered Kinase Neurosciences medicine.disease Neurofibromin 1 eye diseases 3. Good health Brain Disorders nervous system diseases Brain Cancer 030104 developmental biology lcsh:Biology (General) 030220 oncology & carcinogenesis biology.protein Cancer research Cancer development General Agricultural and Biological Sciences business |
| Zdroj: | Communications Biology, Vol 1, Iss 1, Pp 1-11 (2018) Communications biology, vol 1, iss 1 Communications Biology |
| ISSN: | 2399-3642 |
| DOI: | 10.1038/s42003-018-0163-y |
| Popis: | 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. Isakson et al. report a genetically engineered minipig model of Neurofibromatosis Type 1 (NF1) that exhibits clinical hallmarks of the disease, including neurofibromas and optic pathway glioma. This model may expedite the development of imaging methods, biomarkers, and therapies for NF1 patients. |
| Databáze: | OpenAIRE |
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