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
Masonic Cancer Center, University of Minnesota, Room 3-129, Cancer Cardiovascular Research Building, 2231 6th Street SE, Minneapolis, MN, 55455, USA.
Recombinetics Inc., 1246 University Avenue W., Suite 301, St. Paul, MN, 55104, USA.
Commun Biol. 2018 Oct 2;1:158. doi: 10.1038/s42003-018-0163-y. eCollection 2018.
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.
1型神经纤维瘤病（NF1）是一种由（）突变引起的遗传性疾病。NF1患者表现出多种临床表现，且易患癌症。已经开发了许多NF1动物模型，但没有一个能展现出患者所具有的全部疾病谱，这些模型的转化影响有限。我们描述了一种小型猪模型，该模型表现出NF1的临床特征，包括牛奶咖啡斑、神经纤维瘤和视路胶质瘤。在该模型中观察到杂合性的自发缺失，这一现象在NF1患者中也有描述。口服丝裂原活化蛋白激酶/细胞外信号调节激酶抑制剂可抑制Ras信号传导。据我们所知，该模型为研究NF1的复杂生物学和自然史提供了前所未有的机会，并且可能被证明对于成像方法、生物标志物的开发以及NF1靶向治疗的安全性和有效性评估不可或缺。
