GSE160586
Study of the effect of Protein Kinase CK2 alpha prime in the transcriptional deficits associated with Huntington's disease
Protein kinase CK2 alpha prime (CK2a') is preferentially upregulated in the striatum of patients with HD and in different cellular and mouse models of HD. CK2a' happloinsufficiency in the zQ175 HD mouse model restored several HD-like phenotypes. We hypothesized that CK2a' neuronal up-regulation is linked to key transcriptional alterations in the zQ175 mouse model. We found that CK2a' haploinsufficiency rescued the expression of genes associated with synaptogenesis and glutamatergic signaling whose upstream regulator seems to be alpha-synuclein. These transcriptomic studies revealed a conection between CK2a', alpha-synuclein dysfunction and transcriptional changes in key signaling pathways. Overall design: Striatum transcriptional profiles in zQ175 mice with and without one allele of CK2a'. RNA-seq analyses in samples obtained from the striatum of 12-14 months old mice using four different genotypes: WT, CK2a' (+/-), zQ175 and zQ175:CK2a'(+/-). All mice are in the C57BL/6 background. Animals were anesthesized with Avertin and intracardially perfused with Heparin+PBS. Brains were dissected and striatum samples were flash frozen in N2 prior to RNA extraction.