Hippocampus and Hypothalamus RNA-sequencing of WFS1-deficient Mice

Wolfram syndrome is caused by mutations in the WFS1 gene. WFS1 protein dysfunction results in a range of neuroendocrine syndromes and is mostly characterized by juvenile-onset diabetes mellitus and optic atrophy. WFS1 has been shown to participate in membrane trafficking, protein processing and Ca²⁺ homeostasis in the endoplasmic reticulum. Aim of the present study was to find the transcriptomic changes influenced by WFS1 in the hypothalamus and hippocampus using RNA-sequencing. The WFS1-deficient mice were used as a model system to analyze the changes in transcriptional networks. The number of differentially expressed genes between hypothalami of WFS1-deficient (Wfs1KO) and wild-type (WT) mice was 43 and between hippocampi 311 with False Discovery Rate (FDR) <0.05. Avpr1a and Avpr1b were significantly upregulated in the hypothalamus and hippocampus of Wfs1KO mice respectively. Trpm8 was the most upregulated gene in the hippocampus of Wfs1KO mice. The functional analysis revealed significant enrichment of networks and pathways associated with protein synthesis, cell-to-cell signaling and interaction, molecular transport, metabolic disease and nervous system development and function. In conclusion, the transcriptomic profiles of WFS1-deficient hypothalamus and hippocampus do indicate the activation of degenerative molecular pathways causing the clinical occurrences typical to Wolfram syndrome.