HECT Domain Containing Protein 2 (HECTD2)

Hectd2, an E3 ubiquitin ligase, as a quantitative trait gene for prion disease incubation time in mice. An association between HECTD2 haplotypes and susceptibility to the acquired human prion diseases, vCJD and kuru. A genotype-associated differential expression of Hectd2 mRNA in mouse brains and human lymphocytes and a significant up-regulation of transcript in mice at the terminal stage of prion disease. Although the substrate of HECTD2 is unknown, these data highlight the importance of proteosome-directed protein degradation in neurodegeneration. This is the first demonstration of a mouse quantitative trait gene that also influences susceptibility to human prion diseases. Characterisation of such genes is key to understanding human risk and the molecular basis of incubation periods.