基因剔除小鼠
癌症研究
炎症
生物
神经科学
细胞生物学
医学
免疫学
基因
遗传学
作者
Katarzyna J. Radomska,Fanny Coulpier,Aurélie Gresset,Alain Schmitt,Amal Debbiche,Sophie Lemoine,Pierre Wolkenstein,Jean‐Michel Vallat,Patrick Charnay,Piotr Topilko
出处
期刊:Cancer Discovery
[American Association for Cancer Research]
日期:2019-01-01
卷期号:9 (1): 130-147
被引量:55
标识
DOI:10.1158/2159-8290.cd-18-0156
摘要
Abstract Patients carrying an inactive NF1 allele develop tumors of Schwann cell origin called neurofibromas (NF). Genetically engineered mouse models have significantly enriched our understanding of plexiform forms of NFs (pNF). However, this has not been the case for cutaneous neurofibromas (cNF), observed in all NF1 patients, as no previous model recapitulates their development. Here, we show that conditional Nf1 inactivation in Prss56-positive boundary cap cells leads to bona fide pNFs and cNFs. This work identifies subepidermal glia as a likely candidate for the cellular origin of cNFs and provides insights on disease mechanisms, revealing a long, multistep pathologic process in which inflammation-related signals play a pivotal role. This new mouse model is an important asset for future clinical and therapeutic investigations of NF1-associated neurofibromas. Significance: Patients affected by NF1 develop numerous cNFs. We present a mouse model that faithfully recapitulates cNFs, identify a candidate cell type at their origin, analyze the steps involved in their formation, and show that their development is dramatically accelerated by skin injury. These findings have important clinical/therapeutic implications. This article is highlighted in the In This Issue feature, p. 1
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