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:	Fiona B Young, Sonia Franciosi, Amanda Spreeuw, Yu Deng, Shaun Sanders, Natalie C M Tam, Kun Huang, Roshni R Singaraja, Weining Zhang, Nagat Bissada, Chris Kay, Michael R Hayden
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5db8172525484d548ab42c775980e410
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spelling	oai:doaj.org-article:5db8172525484d548ab42c775980e4102021-11-18T07:17:45ZLow levels of human HIP14 are sufficient to rescue neuropathological, behavioural, and enzymatic defects due to loss of murine HIP14 in Hip14-/- mice.1932-620310.1371/journal.pone.0036315https://doaj.org/article/5db8172525484d548ab42c775980e4102012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22649491/?tool=EBIhttps://doaj.org/toc/1932-6203Huntingtin 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.Fiona B YoungSonia FranciosiAmanda SpreeuwYu DengShaun SandersNatalie C M TamKun HuangRoshni R SingarajaWeining ZhangNagat BissadaChris KayMichael R HaydenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e36315 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fiona B Young Sonia Franciosi Amanda Spreeuw Yu Deng Shaun Sanders Natalie C M Tam Kun Huang Roshni R Singaraja Weining Zhang Nagat Bissada Chris Kay Michael R Hayden Low levels of human HIP14 are sufficient to rescue neuropathological, behavioural, and enzymatic defects due to loss of murine HIP14 in Hip14-/- mice.
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.
format	article
author	Fiona B Young Sonia Franciosi Amanda Spreeuw Yu Deng Shaun Sanders Natalie C M Tam Kun Huang Roshni R Singaraja Weining Zhang Nagat Bissada Chris Kay Michael R Hayden
author_facet	Fiona B Young Sonia Franciosi Amanda Spreeuw Yu Deng Shaun Sanders Natalie C M Tam Kun Huang Roshni R Singaraja Weining Zhang Nagat Bissada Chris Kay Michael R Hayden
author_sort	Fiona B Young
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_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_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_sort	low levels of human hip14 are sufficient to rescue neuropathological, behavioural, and enzymatic defects due to loss of murine hip14 in hip14-/- mice.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/5db8172525484d548ab42c775980e410
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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.

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