Gene expression profiles in the striatum of the R6/2 mouse model of Huntington's disease injected with LNA-oligonucleotides complementary to the CAG repeats (LNA-CTG). Mus musculus

We investigated gene expression signatures in the striatum of wild-type mice injected with a control/scrambeled LNA-oligonucleotide (LNA-SCB) and R6/2 mice injected with LNA-SCB or LNA-CTG. Five mice were used per condition. Each group of mice received two consecutive intrastriatal injections of LNA-CTG or LNA-SCB (0.05 nmols per injection, separated by 3 days) at 11 weeks of age , when motor symptoms appeared in the R6/2 mice. Injection of LNA-CTG resulted in a signifficant attenuation of the R6/2 mice motor defficits, as early as one week after administration (12 weeks of age) and persisted for at least 4 additional weeks (15 weeks of age). Overal gene expression in each group was evaluated short before motor improvement was observed (5 days post-injection), to detect gene expression changes and signalling pathway alterations underlying the benefficial effects. Gene expression was assessed with Agilent SurePrint G3 Mouse GE 8 × 60K Microarray. Target genes were validated using real-time quantitative PCR. Overall design: 15 striatal tissue samples were analyzed, using Agilent technology: 5 wild-type, LNA-SCB samples; 5 R6/2, LNA-SCB samples; 5 R6/2, LNA-CTG samples. An internal control sample was included UMRR