Altered palmitoylation and neuropathological deficits in mice lacking HIP14.
Singaraja RR., Huang K., Sanders SS., Milnerwood AJ., Hines R., Lerch JP., Franciosi S., Drisdel RC., Vaid K., Young FB., Doty C., Wan J., Bissada N., Henkelman RM., Green WN., Davis NG., Raymond LA., Hayden MR.
Huntingtin interacting protein 14 (HIP14, ZDHHC17) is a huntingtin (HTT) interacting protein with palmitoyl transferase activity. In order to interrogate the function of Hip14, we generated mice with disruption in their Hip14 gene. Hip14-/- mice displayed behavioral, biochemical and neuropathological defects that are reminiscent of Huntington disease (HD). Palmitoylation of other HIP14 substrates, but not Htt, was reduced in the Hip14-/- mice. Hip14 is dysfunctional in the presence of mutant htt in the YAC128 mouse model of HD, suggesting that altered palmitoylation mediated by HIP14 may contribute to HD.