Open AccessGlobal Rhes knockout in the Q175 Huntington’s disease mouse model
Author(s) -
Taneli Heikkinen,
Timo Bragge,
Juha Kuosmanen,
Teija Parkkari,
Sanna Aila Gustafsson,
Mei Kwan,
José Eduardo Padilla Beltrán,
Afshin Ghavami,
Srinivasa Subramaniam,
Neelam Shahani,
Uri Nimrod Ramírez-Jarquín,
Larry Park,
Ignacio Muñoz-Sanjuán,
Deanna Marchionini
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0258486
Subject(s) - huntingtin , huntington's disease , knockout mouse , biology , gene knockin , autophagy , huntingtin protein , striatum , mutant , polyglutamine tract , microbiology and biotechnology , genetics , neuroscience , gene , medicine , disease , apoptosis , dopamine
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.