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Low Levels of Human HIP14 Are Sufficient to Rescue Neuropathological, Behavioural, and Enzymatic Defects Due to Loss of Murine HIP14 in Hip14−/− Mice

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 (HD). HIP14 palmitoylates a specific set of neuronal substrates critical at the synapse, and dow...

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Autores principales: Young, Fiona B., Franciosi, Sonia, Spreeuw, Amanda, Deng, Yu, Sanders, Shaun, Tam, Natalie C. M., Huang, Kun, Singaraja, Roshni R., Zhang, Weining, Bissada, Nagat, Kay, Chris, Hayden, Michael R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359340/
https://www.ncbi.nlm.nih.gov/pubmed/22649491
http://dx.doi.org/10.1371/journal.pone.0036315
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author Young, Fiona B.
Franciosi, Sonia
Spreeuw, Amanda
Deng, Yu
Sanders, Shaun
Tam, Natalie C. M.
Huang, Kun
Singaraja, Roshni R.
Zhang, Weining
Bissada, Nagat
Kay, Chris
Hayden, Michael R.
author_facet Young, Fiona B.
Franciosi, Sonia
Spreeuw, Amanda
Deng, Yu
Sanders, Shaun
Tam, Natalie C. M.
Huang, Kun
Singaraja, Roshni R.
Zhang, Weining
Bissada, Nagat
Kay, Chris
Hayden, Michael R.
author_sort Young, Fiona B.
collection PubMed
description 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 (HD). 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. We previously reported that mice lacking murine Hip14 (Hip14−/−) share features of HD. In the current study, we have generated human HIP14 BAC transgenic mice and crossed them to the Hip14−/− model in order to confirm that the defects seen in Hip14−/− mice are in fact due to loss of Hip14. In addition, we sought to determine whether human HIP14 can provide functional compensation for loss of murine Hip14. We demonstrate that despite a relative low level of expression, as assessed via Western blot, BAC-derived human HIP14 compensates for deficits in neuropathology, behavior, and PAT enzyme function seen in the Hip14−/− model. Our findings yield important insights into HIP14 function in vivo.
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spelling pubmed-33593402012-05-30 Low Levels of Human HIP14 Are Sufficient to Rescue Neuropathological, Behavioural, and Enzymatic Defects Due to Loss of Murine HIP14 in Hip14−/− Mice Young, Fiona B. Franciosi, Sonia Spreeuw, Amanda Deng, Yu Sanders, Shaun Tam, Natalie C. M. Huang, Kun Singaraja, Roshni R. Zhang, Weining Bissada, Nagat Kay, Chris Hayden, Michael R. PLoS One Research Article 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 (HD). 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. We previously reported that mice lacking murine Hip14 (Hip14−/−) share features of HD. In the current study, we have generated human HIP14 BAC transgenic mice and crossed them to the Hip14−/− model in order to confirm that the defects seen in Hip14−/− mice are in fact due to loss of Hip14. In addition, we sought to determine whether human HIP14 can provide functional compensation for loss of murine Hip14. We demonstrate that despite a relative low level of expression, as assessed via Western blot, BAC-derived human HIP14 compensates for deficits in neuropathology, behavior, and PAT enzyme function seen in the Hip14−/− model. Our findings yield important insights into HIP14 function in vivo. Public Library of Science 2012-05-23 /pmc/articles/PMC3359340/ /pubmed/22649491 http://dx.doi.org/10.1371/journal.pone.0036315 Text en Young et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Young, Fiona B.
Franciosi, Sonia
Spreeuw, Amanda
Deng, Yu
Sanders, Shaun
Tam, Natalie C. M.
Huang, Kun
Singaraja, Roshni R.
Zhang, Weining
Bissada, Nagat
Kay, Chris
Hayden, Michael R.
Low Levels of Human HIP14 Are Sufficient to Rescue Neuropathological, Behavioural, and Enzymatic Defects Due to Loss of Murine HIP14 in Hip14−/− Mice
title Low Levels of Human HIP14 Are Sufficient to Rescue Neuropathological, Behavioural, and Enzymatic Defects Due to Loss of Murine HIP14 in Hip14−/− Mice
title_full Low Levels of Human HIP14 Are Sufficient to Rescue Neuropathological, Behavioural, and Enzymatic Defects Due to Loss of Murine HIP14 in Hip14−/− Mice
title_fullStr Low Levels of Human HIP14 Are Sufficient to Rescue Neuropathological, Behavioural, and Enzymatic Defects Due to Loss of Murine HIP14 in Hip14−/− Mice
title_full_unstemmed Low Levels of Human HIP14 Are Sufficient to Rescue Neuropathological, Behavioural, and Enzymatic Defects Due to Loss of Murine HIP14 in Hip14−/− Mice
title_short Low Levels of Human HIP14 Are Sufficient to Rescue Neuropathological, Behavioural, and Enzymatic Defects Due to Loss of Murine HIP14 in Hip14−/− Mice
title_sort low levels of human hip14 are sufficient to rescue neuropathological, behavioural, and enzymatic defects due to loss of murine hip14 in hip14−/− mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359340/
https://www.ncbi.nlm.nih.gov/pubmed/22649491
http://dx.doi.org/10.1371/journal.pone.0036315
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