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

Neurofibromatosis Type 1 (NF1) is a genetic disease caused by mutations in ( ). 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 tran...

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Published in:Communications biology 2018-01, Vol.1 (1), p.158-158, Article 158
Main Authors: Isakson, Sara H, Rizzardi, Anthony E, Coutts, Alexander W, Carlson, Daniel F, Kirstein, Mark N, Fisher, James, Vitte, Jeremie, Williams, Kyle B, Pluhar, G Elizabeth, Dahiya, Sonika, Widemann, Brigitte C, Dombi, Eva, Rizvi, Tilat, Ratner, Nancy, Messiaen, Ludwine, Stemmer-Rachamimov, Anat O, Fahrenkrug, Scott C, Gutmann, David H, Giovannini, Marco, Moertel, Christopher L, Largaespada, David A, Watson, Adrienne L
Format: Article
Language:English
Subjects:
Animal models
Biology
Biomarkers
Enzyme inhibitors
Extracellular signal-regulated kinase
Genetic disorders
Genetic engineering
Glioma
Heterozygosity
Kinases
Loss of heterozygosity
MAP kinase
Neurofibromatosis
Neurofibromin 1
Neurological disorders
Oral administration
Protein kinase
Recklinghausen's disease
Tumors
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Summary:Neurofibromatosis Type 1 (NF1) is a genetic disease caused by mutations in ( ). 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.
ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-018-0163-y