Braf-mutant Schwann cells divert to a repair phenotype to induce congenital demyelinating neuropathy [ScN]

RASopathies are a diverse group of developmental disorders associated with germline or somatic mutations in genes of the Mitogen Activated Protein Kinase (MAPK) signaling pathway. We characterized in this dataset a mosaic mouse model, in which a constitutively active form of the MAPK effector Braf (V600E) is expressed in the embryonic progenitors of myelin-forming Schwann cells of peripheral nerves under the control of the MpZ(P0)-Cre recombinase. These mice develop an early, fully penetrant degenerative peripheral neuropathy. The RNAseq experiment compares total RNA extracted from whole sciatic nerves between spinal cord and knee between mutant and control pairs of littermates from six distinct outbred litters at postnatal day 21. We performed RNA-seq to compare four mutant whole sciatic nerves to four control littermate sciatic nerves at two different postnatal stages. After aligning sequences to the mouse genome, we undertook differential gene expression analysis.RAS相关疾病（RASopathies）是一类多样化的发育障碍类群，其发病与丝裂原活化蛋白激酶（Mitogen Activated Protein Kinase，MAPK）信号通路相关基因的生殖系或体细胞突变密切相关。本数据集所表征的嵌合小鼠模型，在MpZ(P0)-Cre重组酶（MpZ(P0)-Cre recombinase）的调控下，于外周神经中形成髓鞘的施万细胞（Schwann cells）的胚胎祖细胞内，表达MAPK效应分子BRAF（V600E）的组成型激活形式。该模型小鼠会早期出现完全外显的退行性外周神经病变。本RNA测序（RNA-seq）实验比较了出生后第21天、来自6个独立远交系幼崽的突变型与同窝野生型对照小鼠的、取自脊髓至膝关节区段的整条坐骨神经中的总RNA。我们进一步开展了RNA-seq实验，对两个不同出生后阶段的4根突变型坐骨神经与4根同窝野生型对照坐骨神经进行比较分析。在将测序序列比对至小鼠基因组后，我们完成了差异基因表达分析。