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The biology and expression of huntingtin interacting protein 14

University of British Columbia

Huntingtin Interacting Protein 14 (HIP14) is a palmitoyl acyl transferase (PAT) that was first identified due to altered interaction with mutant huntingtin, the protein responsible for Huntington Disease. HIP14 palmitoylates a specific set of neuronal substrates critical at the synapse, and downregulation of HIP14 by siRNA in vitro results in increased cell death in neurons. Recent findings have revealed that mice lacking murine Hip14 (Hip14-/-) demonstrate a Huntington- Disease-like phenotype. In the current study, we have generated and characterized human HIP14 BAC transgenic mice. We generated humanized HIP14 transgenic mice by crossing the HIP14 BAC mouse to the Hip14-/- model. Rescue of the Hip14-/- phenotype indicates that the defects seen in Hip14-/- mice are in fact due to loss of HIP14. In addition, our findings indicate human HIP14 can compensate for the loss of the murine ortholog, and that very low levels of HIP14 are sufficient to rescue the Hip14-/- phenotype. Finally, we assess patterns of HIP14 expression in early development. Our findings further our understanding of HIP14 in vivo, and point to several potential avenues for future studies.

Text

2012-09-01

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/37091

Medical Genetics

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/