PDF(Pubmed)
Abstract：
Neurofibromatosis Type I (NF1) is a rare genetic disorder. NF1 patients frequently develop a benign tumor in peripheral nerve plexuses called plexiform neurofibroma. In the past two decades, tissue-specific Nf1 knockout mouse models were developed using commercially available tissue-specific Cre recombinase and the Nf1 flox mice to mimic neurofibroma development. However, these models develop para-spinal neurofibroma, recapitulating a rare type of neurofibroma found in NF1 patients. The NPcis mouse model developed a malignant version of neurofibroma called malignant peripheral nerve sheath tumor (MPNST) within 3 to 6 months but intriguingly without apparent benign precursor lesion. Here, we revisited the NPcis model and discovered that about 20% display clinical signs similar to Nf1 tissue-specific knockout mice models. However, a systematic histological analysis could not explain the clinical signs we observed although we noticed lesions reminiscent of a neurofibroma in a peripheral nerve, a cutaneous neurofibroma, and para-spinal neurofibroma on rare occasions in NPcis mice. We also observed that 10% of the mice developed a malignant peripheral nerve sheath tumor (MPNST) spontaneously, coinciding with their earring tag identification. Strikingly, half of the sciatic nerves from NPcis mice developed plexiform neurofibroma within 1-6 months when intentionally injured. Thus, we provided a procedure to turn the widely used NPcis sarcoma model into a model recapitulating plexiform neurofibroma.
摘要：
神经纤维瘤病I型（NF1）是一种罕见的遗传性疾病。NF1患者经常在周围神经丛形成良性肿瘤，称为丛状神经纤维瘤。在过去的二十年里，使用市售的组织特异性Cre重组酶和Nf1flox小鼠开发了组织特异性Nf1敲除小鼠模型，以模拟神经纤维瘤的发展。然而,这些模型发展成脊髓旁神经纤维瘤，在NF1患者中发现了一种罕见的神经纤维瘤。NPcis小鼠模型在3至6个月内发展出恶性形式的神经纤维瘤，称为恶性周围神经鞘瘤（MPNST），但有趣的是没有明显的良性前体病变。这里,我们再次观察了NPcis模型,发现约20%的小鼠表现出与Nf1组织特异性基因敲除小鼠模型相似的临床症状.然而,系统的组织学分析不能解释我们观察到的临床症状，尽管我们注意到周围神经损伤让人联想到神经纤维瘤，皮肤神经纤维瘤,在罕见的NPcis小鼠中出现脊髓旁神经纤维瘤。我们还观察到10％的小鼠自发发生恶性外周神经鞘瘤（MPNST），与他们的耳环标签识别相吻合。引人注目的是，NPcis小鼠坐骨神经的一半在1-6个月内发生了丛状神经纤维瘤。因此，我们提供了将广泛使用的NPcis肉瘤模型转变为重述丛状神经纤维瘤的模型的方法.
