Global Rhes knockout in the Q175 Huntington's disease mouse model.
Huntington's disease (HD) results from an expansion mutation in the polyglutamine tract in huntingtin. Although huntingtin is ubiquitously expressed in the body, the striatum suffers the most severe pathology. Rhes is a Ras-related small GTP-binding protein highly expressed in the striatum that...
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2021
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oai:doaj.org-article:5d08393a3e9247bea54802339f2736c82021-12-02T20:19:12ZGlobal Rhes knockout in the Q175 Huntington's disease mouse model.1932-620310.1371/journal.pone.0258486https://doaj.org/article/5d08393a3e9247bea54802339f2736c82021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258486https://doaj.org/toc/1932-6203Huntington's disease (HD) results from an expansion mutation in the polyglutamine tract in huntingtin. Although huntingtin is ubiquitously expressed in the body, the striatum suffers the most severe pathology. Rhes is a Ras-related small GTP-binding protein highly expressed in the striatum that has been reported to modulate mTOR and sumoylation of mutant huntingtin to alter HD mouse model pathogenesis. Reports have varied on whether Rhes reduction is desirable for HD. Here we characterize multiple behavioral and molecular endpoints in the Q175 HD mouse model with genetic Rhes knockout (KO). Genetic RhesKO in the Q175 female mouse resulted in both subtle attenuation of Q175 phenotypic features, and detrimental effects on other kinematic features. The Q175 females exhibited measurable pathogenic deficits, as measured by MRI, MRS and DARPP32, however, RhesKO had no effect on these readouts. Additionally, RhesKO in Q175 mixed gender mice deficits did not affect mTOR signaling, autophagy or mutant huntingtin levels. We conclude that global RhesKO does not substantially ameliorate or exacerbate HD mouse phenotypes in Q175 mice.Taneli HeikkinenTimo BraggeJuha KuosmanenTeija ParkkariSanna GustafssonMei KwanJose BeltranAfshin GhavamiSrinivasa SubramaniamNeelam ShahaniUri Nimrod Ramírez-JarquínLarry ParkIgnacio Muñoz-SanjuánDeanna M MarchioniniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258486 (2021) |
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Medicine R Science Q Taneli Heikkinen Timo Bragge Juha Kuosmanen Teija Parkkari Sanna Gustafsson Mei Kwan Jose Beltran Afshin Ghavami Srinivasa Subramaniam Neelam Shahani Uri Nimrod Ramírez-Jarquín Larry Park Ignacio Muñoz-Sanjuán Deanna M Marchionini Global Rhes knockout in the Q175 Huntington's disease mouse model. |
| description |
Huntington's disease (HD) results from an expansion mutation in the polyglutamine tract in huntingtin. Although huntingtin is ubiquitously expressed in the body, the striatum suffers the most severe pathology. Rhes is a Ras-related small GTP-binding protein highly expressed in the striatum that has been reported to modulate mTOR and sumoylation of mutant huntingtin to alter HD mouse model pathogenesis. Reports have varied on whether Rhes reduction is desirable for HD. Here we characterize multiple behavioral and molecular endpoints in the Q175 HD mouse model with genetic Rhes knockout (KO). Genetic RhesKO in the Q175 female mouse resulted in both subtle attenuation of Q175 phenotypic features, and detrimental effects on other kinematic features. The Q175 females exhibited measurable pathogenic deficits, as measured by MRI, MRS and DARPP32, however, RhesKO had no effect on these readouts. Additionally, RhesKO in Q175 mixed gender mice deficits did not affect mTOR signaling, autophagy or mutant huntingtin levels. We conclude that global RhesKO does not substantially ameliorate or exacerbate HD mouse phenotypes in Q175 mice. |
| format |
article |
| author |
Taneli Heikkinen Timo Bragge Juha Kuosmanen Teija Parkkari Sanna Gustafsson Mei Kwan Jose Beltran Afshin Ghavami Srinivasa Subramaniam Neelam Shahani Uri Nimrod Ramírez-Jarquín Larry Park Ignacio Muñoz-Sanjuán Deanna M Marchionini |
| author_facet |
Taneli Heikkinen Timo Bragge Juha Kuosmanen Teija Parkkari Sanna Gustafsson Mei Kwan Jose Beltran Afshin Ghavami Srinivasa Subramaniam Neelam Shahani Uri Nimrod Ramírez-Jarquín Larry Park Ignacio Muñoz-Sanjuán Deanna M Marchionini |
| author_sort |
Taneli Heikkinen |
| title |
Global Rhes knockout in the Q175 Huntington's disease mouse model. |
| title_short |
Global Rhes knockout in the Q175 Huntington's disease mouse model. |
| title_full |
Global Rhes knockout in the Q175 Huntington's disease mouse model. |
| title_fullStr |
Global Rhes knockout in the Q175 Huntington's disease mouse model. |
| title_full_unstemmed |
Global Rhes knockout in the Q175 Huntington's disease mouse model. |
| title_sort |
global rhes knockout in the q175 huntington's disease mouse model. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/5d08393a3e9247bea54802339f2736c8 |
| work_keys_str_mv |
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