Transcriptional profiling of striatum and cortex from a LacO-Q140 inducible mouse model of Huntington’s disease with early and late mutant HTT lowering

Inducible mutant huntingtin mice were genetically engineered by introducing the lac operon sequence (LacO) into the Q140 promoter of the Q140 KI mice. LacO-140Q mice were then crossed to transgenic Lac repressor protein (LacIR) mice. LacIR occupies the LacO sequence in the promoter and thereby blocks transcription of Q140. Beta-galactoside analog isopropyl thiogalactoside (IPTG) binds to LacIR, which results in decreased affinity between the repressor and operator, thereby relieving repression. All mice in this study have the LacIR transgene, therefore the default state of the mouse containing LacOQ140;LacIR is maximal repression of Q140. CHDI generated and analyzed RNASeq data from inducible LacOQ140 mice at 2 points: 6 and 12 months. Transcriptional profiling in the striatum and cortex with early versus late mutant HTT lowering is detailed. Hdh(LacO-140Q/+):β-actin-LacIR tg or Hdh(LacO-+/+):β-actin-LacIR tg wild-type mice received either no treatment or ОІ-D-1-Thiogalactopyranoside (IPTG) treatment starting at E5 and continued to 2 months or 8 months of age or throughout life. RNASeq analysis was performed on samples from the striatum and cortex at 6 and 12 months of age. N = 10 per group (5F/5M). There are 4 groups at 6 months of age and 5 groups at 12 months of age.