HECTD2 Is Associated with Susceptibility to Mouse and Human Prion Disease
Figure 1
Quantitative RT-PCR of Hectd2I.
cDNA was prepared from whole brains of uninfected 8 week old male mice or mice at the terminal stages of disease following intracerebral inoculation with Chandler/RML mouse-adapted scrapie prions. All samples were duplexed for Hectd2 and GAPDH fluorogenic probes and run in triplicate with n = 6 for each mouse strain/group. Mean±s.e.m. Hectd2 mRNA expression level is expressed in arbitrary units as normalised by the quantity of GAPDH (y-axis). A, Inbred strains are grouped according to the major strain distribution pattern seen in Hectd2 (Group A = A, AKR, BALB; Group B = C3H, C57, CBA, DBA). Expression was ×2.4 greater in group A than group B (P = 2.85×10−9, unpaired t-test). B, Comparison of Hectd2 expression in normal and RML prion-infected C57BL6 mouse brains. Expression was ×5.0 greater in the brains of prion-infected mice, (P = 2.66×10−8, unpaired t-test). C, Expression of HECTD2 in cDNA prepared from lymphocytes of human blood donors (n = 140). Samples were duplexed for HECTD2 and β-actin fluorogenic probes and run four times. Mean±s.e.m. HECTD2 mRNA expression level is expressed in arbitrary units as normalised by the quantity of β-actin (y-axis). Data are grouped according to genotypes at rs12249854 as determined from genomic DNA. Expression was ×2.3 greater in the heterozygotes (TA) than for the major allele homozygotes (TT) (P = 0.0008 Mann-Whitney test).