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Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by a CAG repeat expansion within exon 1 of the huntingtin ( HTT ) gene.  HTT  mRNA contains 67 exons and does not always splice between exon 1 and exon 2 leading to the production of a small polyadenylated  HTTexon 1 transcript, and the full-length  HTT  mRNA has three 3′UTR isoforms. We have developed a QuantiGene multiplex panel for the simultaneous detection of all of these mouse  Htt  transcripts directly from tissue lysates and demonstrate that this can replace the more work-intensive Taqman qPCR assays. We have applied this to the analysis of brain regions from the zQ175 HD mouse model and wild type littermates at two months of age. We show that the incomplete splicing of  Htt  occurs throughout the brain and confirm that this originates from the mutant and not endogenous  Htt  allele. Given that  HTTexon 1 encodes the highly pathogenic exon 1 HTT protein, it is essential that the levels of all  Htt  transcripts can be monitored when evaluating HTT lowering approaches. Our QuantiGene panel will allow the rapid comparative assessment of all  Htt  transcripts in cell lysates and mouse tissues without the need to first extract RNA.

Extensive Expression Analysis of Htt Transcripts in Brain Regions from the zQ175 HD Mouse Model Using a QuantiGene Multiplex Assay