B011 Transcriptomic analysis of transgenic minipig model of Huntington’s disease

<h3>Background</h3> The transgenic minipig model (TgHD) bearing part of the human huntingtin gene was established in 2009. Since then, the TgHD model has been studied for molecular expression changes on cellular and tissue levels. Nevertheless, specific brain region transcriptome data were missing. <h3>Aim</h3> Obtain transcriptomic profile of TgHD minipigs at 4 and 8 years and compare to their WT siblings. Analyze gene expression at intermediate and late stages of disease in the minipig model and find new insights into huntingtin pathology in the porcine brain. <h3>Methods</h3> RNA-seq of putamen from heterozygotic transgenic and wild-type minipig model of 4 and 8 years (n=3). Further validation of results was done by qPCR. Moreover, cytokine levels were measured in CSF. Outcomes: More than 2500 differentially expressed genes (DEGs) were detected in 8 yo TgHD minipigs, while only 5 DEGs were detected in the group of 4-year-old pigs. Several pathways catalogued in WikiPathways are dysregulated, such as pathways for calcium regulation, MAPK signalling and BDNF signalling, pointing to changes in cellular signalling, synaptic functions and neuronal survival. <h3>Conclusions</h3> 8yo but not 4yo TgHD minipig RNA seq shows robust gene expression dysregulation, indicating the relatively late onset of disease symptoms.