AW495222 UP in 'R6/2' vs 'wild type genotype'
(Factor value) GENOTYPE/wild type genotype
Arpp21 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Tex40 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Lgr5 UP in 'HDAC4het' vs 'wild type genotype'
Nsg2 UP in 'R6/2::HDAC4het' vs 'wild type genotype'
Plk5 DOWN in 'R6/2' vs 'wild type genotype'
Eomes UP in 'HDAC4het' vs 'wild type genotype'
Pttg1 UP in 'R6/2::HDAC4het' vs 'wild type genotype'
Myo7a UP in 'HDAC4het' vs 'wild type genotype'
Myh7 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Rgs4 DOWN in 'R6/2' vs 'wild type genotype'
Pde10a DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Dmrt2 UP in 'R6/2' vs 'wild type genotype'
A330076H08Rik DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Prps1l3 UP in 'R6/2::HDAC4het' vs 'wild type genotype'
Brca1 UP in 'R6/2' vs 'wild type genotype'
Lemd1 DOWN in 'R6/2' vs 'wild type genotype'
Brca1 UP in 'R6/2::HDAC4het' vs 'wild type genotype'
Rspo1 DOWN in 'R6/2' vs 'wild type genotype'
Penk DOWN in 'R6/2' vs 'wild type genotype'
Gpr83 DOWN in 'R6/2' vs 'wild type genotype'
Ddit4l DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Stard8 DOWN in 'R6/2' vs 'wild type genotype'
Pbx3 UP in 'HDAC4het' vs 'wild type genotype'
RP24-439I22.1 UP in 'R6/2::HDAC4het' vs 'wild type genotype'
Ifit1 UP in 'R6/2' vs 'wild type genotype'
Phka2 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Ryr1 DOWN in 'R6/2' vs 'wild type genotype'
Cartpt DOWN in 'R6/2' vs 'wild type genotype'
Scn4b DOWN in 'R6/2' vs 'wild type genotype'
Vps37a UP in 'R6/2' vs 'wild type genotype'
Phka2 DOWN in 'R6/2' vs 'wild type genotype'
Rgs4 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Gm12300 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Gpr83 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
R3hdm1 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Ptpn20 UP in 'R6/2' vs 'wild type genotype'
Onecut2 UP in 'R6/2' vs 'wild type genotype'
Plcb1 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Malat1 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Dlgap2 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Npas4 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Tpx2 UP in 'R6/2' vs 'wild type genotype'
Hfe2 DOWN in 'R6/2' vs 'wild type genotype'
Vip DOWN in 'R6/2' vs 'wild type genotype'
Itpka DOWN in 'R6/2' vs 'wild type genotype'
Camk4 DOWN in 'R6/2' vs 'wild type genotype'
Ptpn20 UP in 'R6/2::HDAC4het' vs 'wild type genotype'
Crh DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Th UP in 'HDAC4het' vs 'wild type genotype'
Dmkn DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Mid1 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Gpr153 DOWN in 'R6/2' vs 'wild type genotype'
Apc DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Pdyn DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Analysis of 'R6/2' vs 'wild type genotype'
Histone deacetylase (HDAC) 4 is a transcriptional repressor that contains a glutamine rich domain. We hypothesised that it may be involved in the molecular pathogenesis of Huntington's disease (HD), a protein folding neurodegenerative disorder caused by an aggregation-prone polyglutamine expansion and transcriptional dysregulation. We found that HDAC4 interacts with huntingtin in a polyglutamine-length dependent manner and co-localises with cytoplasmic inclusions. We show that HDAC4 reduction delayed cytoplasmic aggregate formation, restored Bdnf transcript levels and rescued neuronal and cortico-striatal synaptic function in HD mouse models. This was accompanied by an improvement in motor co-ordination, neurological phenotypes and increased lifespan. Surprisingly, HDAC4 reduction had no effect on global transcriptional dysfunction and did not modulate nuclear huntingtin aggregation. Our results define a crucial role for cytoplasmic aggregation in the molecular pathology of HD. HDAC4 reduction presents a novel strategy for targeting huntingtin aggregation which may be amenable to small molecule therapeutics. mRNA expression analysis was performed by microarray in 9 weeks old WT (n=9), R6/2 (n=9), HDAC4het (n=9) and Double R6/2::HDAC4het (n=10) mice. Microarray quality control was performed using the software package provided on RACE (http://race.unil.ch).
Fam168a UP in 'HDAC4het' vs 'wild type genotype'
Abi3bp DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Fst DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Kcnj9 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Egr2 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Scn9a UP in 'R6/2::HDAC4het' vs 'wild type genotype'
Ddit4l DOWN in 'R6/2' vs 'wild type genotype'
Ppp1r1b DOWN in 'R6/2' vs 'wild type genotype'
Myl4 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Gpr153 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Ovgp1 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Dmkn DOWN in 'R6/2' vs 'wild type genotype'
Tnnc1 DOWN in 'R6/2' vs 'wild type genotype'
Nptx2 DOWN in 'R6/2' vs 'wild type genotype'
RP24-439I22.1 UP in 'R6/2' vs 'wild type genotype'
Palm2 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Rasl10a DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
H2-D1 UP in 'R6/2::HDAC4het' vs 'wild type genotype'
Npy2r DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Cks1b UP in 'R6/2::HDAC4het' vs 'wild type genotype'
AW495222 UP in 'R6/2::HDAC4het' vs 'wild type genotype'
Slc1a2 DOWN in 'R6/2' vs 'wild type genotype'
Ryr1 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Wisp1 UP in 'HDAC4het' vs 'wild type genotype'
Cplx3 DOWN in 'R6/2' vs 'wild type genotype'
Qk DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Camk2n1 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Sfmbt2 UP in 'R6/2' vs 'wild type genotype'
Myl4 DOWN in 'R6/2' vs 'wild type genotype'
Shisa3 UP in 'HDAC4het' vs 'wild type genotype'
Nrep DOWN in 'R6/2' vs 'wild type genotype'
Npas4 DOWN in 'R6/2' vs 'wild type genotype'
Gm26917 DOWN in 'R6/2' vs 'wild type genotype'
Vip DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Tnfrsf25 DOWN in 'R6/2' vs 'wild type genotype'
Sst DOWN in 'R6/2' vs 'wild type genotype'
Homer1 DOWN in 'R6/2' vs 'wild type genotype'
Cnksr2 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Hfe2 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Tex40 DOWN in 'R6/2' vs 'wild type genotype'
Rgs13 UP in 'R6/2::HDAC4het' vs 'wild type genotype'
Egr2 DOWN in 'R6/2' vs 'wild type genotype'
S100a5 UP in 'HDAC4het' vs 'wild type genotype'
Nsg2 UP in 'R6/2' vs 'wild type genotype'
Tbx21 UP in 'HDAC4het' vs 'wild type genotype'
Onecut2 UP in 'R6/2::HDAC4het' vs 'wild type genotype'
Ifi27l2a UP in 'R6/2' vs 'wild type genotype'
Twist1 UP in 'R6/2::HDAC4het' vs 'wild type genotype'
9230110C19Rik DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Pou4f1 UP in 'R6/2' vs 'wild type genotype'
Sst DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Kctd14 UP in 'HDAC4het' vs 'wild type genotype'
Asap1 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Tnnc1 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Abi3bp DOWN in 'R6/2' vs 'wild type genotype'
Fam19a1 DOWN in 'R6/2' vs 'wild type genotype'
Tpx2 UP in 'R6/2::HDAC4het' vs 'wild type genotype'
Dio2 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Enkur UP in 'R6/2' vs 'wild type genotype'
Sostdc1 DOWN in 'HDAC4het' vs 'wild type genotype'
Analysis of 'HDAC4het' vs 'wild type genotype'
Ovgp1 DOWN in 'R6/2' vs 'wild type genotype'
Lemd1 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Fst DOWN in 'R6/2' vs 'wild type genotype'
Crh DOWN in 'R6/2' vs 'wild type genotype'
Prss22 DOWN in 'R6/2' vs 'wild type genotype'
A830010M20Rik DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Ppp1r1b DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Ptgs2 DOWN in 'R6/2' vs 'wild type genotype'
Capn10 UP in 'R6/2::HDAC4het' vs 'wild type genotype'
Oasl2 UP in 'R6/2' vs 'wild type genotype'
Ier5l DOWN in 'R6/2' vs 'wild type genotype'
Myh7 DOWN in 'R6/2' vs 'wild type genotype'
Rasl10a DOWN in 'R6/2' vs 'wild type genotype'
Nos1ap DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Gfra2 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Abi3bp UP in 'HDAC4het' vs 'wild type genotype'
Sfmbt2 UP in 'R6/2::HDAC4het' vs 'wild type genotype'
Lamp5 DOWN in 'R6/2' vs 'wild type genotype'
BC030499 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Fzd3 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Zfp800 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Homer1 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Ptgs2 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Nktr DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Arc DOWN in 'R6/2' vs 'wild type genotype'
Gm12300 DOWN in 'R6/2' vs 'wild type genotype'
Arpp21 DOWN in 'R6/2' vs 'wild type genotype'
Arpp19 DOWN in 'R6/2' vs 'wild type genotype'
Ano3 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Scn9a UP in 'R6/2' vs 'wild type genotype'
Camk2n1 DOWN in 'R6/2' vs 'wild type genotype'
Arc DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Sp8 UP in 'HDAC4het' vs 'wild type genotype'
Nfya UP in 'R6/2::HDAC4het' vs 'wild type genotype'
Gabrd DOWN in 'R6/2' vs 'wild type genotype'
Cdhr1 UP in 'HDAC4het' vs 'wild type genotype'
Ighm DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Otof DOWN in 'R6/2' vs 'wild type genotype'
Nhsl2 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Arhgap32 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
1810022K09Rik UP in 'R6/2' vs 'wild type genotype'
Plk5 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Crhbp DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Penk DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Prps1l3 UP in 'R6/2' vs 'wild type genotype'
A330076H08Rik DOWN in 'R6/2' vs 'wild type genotype'
Gm10010 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Slc1a2 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
(Sample) clinical information/Huntington's disease mouse model
Pou4f1 UP in 'R6/2::HDAC4het' vs 'wild type genotype'
Cks1b UP in 'R6/2' vs 'wild type genotype'
Lamp5 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Crhbp DOWN in 'R6/2' vs 'wild type genotype'
Twist1 UP in 'R6/2' vs 'wild type genotype'
Ankrd63 DOWN in 'R6/2' vs 'wild type genotype'
Analysis of 'R6/2::HDAC4het' vs 'wild type genotype'
Ier5l DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Tulp4 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Npy2r DOWN in 'R6/2' vs 'wild type genotype'
Cartpt DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Rgs13 UP in 'R6/2' vs 'wild type genotype'
Nmb UP in 'HDAC4het' vs 'wild type genotype'
Rph3a DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Nptx2 DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Scn4b DOWN in 'R6/2::HDAC4het' vs 'wild type genotype'
Camkk2 DOWN in 'R6/2' vs 'wild type genotype'