Pluto Bioinformatics

GSE101808: Neuregulin 1 type III reduces severity in a mouse model of Congenital Hypomyelination Neuropathy

Bulk RNA sequencing

Purpose: We hypothesised that neuregulin 1 type III would reverse CHN. Using a faithful mouse model of CHN, we rescued the myelination defects by activation of Nrg1 type III. Unexpectedly, rescue did not depend on upregulation of Egr2 or major myelin genes. Therefore we asked whether we could identify any transcriptomic signature of the canonical pathways downstream of Nrg1 type III that could explain the increase in myelination in the sciatic nerve.; Methods: Sciatic nerve mRNA profiles of 30-day-old wild-type (WT), P0 mutant (Q215X/+), trangenic HA-NRG1 type III, and HA-NRG1 type III:Q215X mice were generated by deep sequencing, in duplicate, using Illumina HiSeq2500 . The sequence reads that passed quality filters were aligned to the mouse reference genome (mm10) with the transcript annotation (UCSC mm10 annotation download from TopHat website) using TopHat (v2.0.9). Quantification for the gene expression and differential expression analysis were done by the software Cufflinks (v2.2.0).; Results: A comprehensive transcriptomic analysis of signals downstream of neuregulin 1 type III in rescued CHN nerves revealed imbalanced activation of MAPK/ERK signals and minor myelin genes, such as Pmp2 and Omg.; Conclusions: Our findings demonstrate that although augmented Nrg1 type III activity modifies the composition of myelin, it still promotes thicker myelin and ameliorates nerve conduction velocity in a mouse model of CHN. Controlled increase of Nrg1 type III activity may be a therapeutic strategy in some hypomyelinating neuropathies. SOURCE: Jie WangNY State Center of Excellence in Bioinformatics & Life Sciences University at Buffalo

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