scholarly journals Cortical Axonal Secretion of BDNF in the Striatum Is Disrupted in the Mutant-huntingtin Knock-in Mouse Model of Huntington's Disease

2018 ◽  
Vol 27 (3) ◽  
pp. 217-225 ◽  
Author(s):  
Hyungju Park
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mutant Huntingtin

scholarly journals Caspase-6 does not contribute to the proteolysis of mutant huntingtin in the HdhQ150 knock-in mouse model of Huntington’s disease

PLoS Currents ◽  
2012 ◽  
Vol 4 ◽  
pp. e4fd085bfc9973 ◽  
Author(s):  
Christian Landles ◽  
Andreas Weiss ◽  
Sophie Franklin ◽  
David Howland ◽  
Gill Bates
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mutant Huntingtin ◽  
Caspase 6

scholarly journals Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington's disease

2014 ◽  
Vol 20 (5) ◽  
pp. 536-541 ◽  
Author(s):  
Nan Wang ◽  
Michelle Gray ◽  
Xiao-Hong Lu ◽  
Jeffrey P Cantle ◽  
Sandra M Holley ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mutant Huntingtin

scholarly journals A YAC Mouse Model for Huntington’s Disease with Full-Length Mutant Huntingtin, Cytoplasmic Toxicity, and Selective Striatal Neurodegeneration

Neuron ◽  
1999 ◽  
Vol 23 (1) ◽  
pp. 181-192 ◽  
Author(s):  
J.Graeme Hodgson ◽  
Nadia Agopyan ◽  
Claire-Anne Gutekunst ◽  
Blair R Leavitt ◽  
Fred LePiane ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Full Length ◽  
Mutant Huntingtin

scholarly journals Global Rhes knockout in the Q175 Huntington’s disease mouse model

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258486
Author(s):  
Taneli Heikkinen ◽  
Timo Bragge ◽  
Juha Kuosmanen ◽  
Teija Parkkari ◽  
Sanna Gustafsson ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
The Body ◽  
Mutant Huntingtin ◽  
Polyglutamine Tract ◽  
Severe Pathology ◽  
Expansion Mutation ◽  
Q175 Mice ◽  
Mixed Gender

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.

scholarly journals Synthetic lethal screening in the mammalian central nervous system identifies Gpx6 as a modulator of Huntington’s disease

2014 ◽  
Vol 112 (1) ◽  
pp. 268-272 ◽  
Author(s):  
Reut Shema ◽  
Ruth Kulicke ◽  
Glenn S. Cowley ◽  
Rachael Stein ◽  
David E. Root ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Model ◽  
Neurodegenerative Disease ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Model Organisms ◽  
Mutant Huntingtin ◽  
Synthetic Lethal ◽  
Mammalian Central Nervous System

Huntington’s disease, the most common inherited neurodegenerative disease, is characterized by a dramatic loss of deep-layer cortical and striatal neurons, as well as morbidity in midlife. Human genetic studies led to the identification of the causative gene, huntingtin. Recent genomic advances have also led to the identification of hundreds of potential interacting partners for huntingtin protein and many hypotheses as to the molecular mechanisms whereby mutant huntingtin leads to cellular dysfunction and death. However, the multitude of possible interacting partners and cellular pathways affected by mutant huntingtin has complicated efforts to understand the etiology of this disease, and to date no curative therapeutic exists. To address the general problem of identifying the disease-phenotype contributing genes from a large number of correlative studies, here we develop a synthetic lethal screening methodology for the mammalian central nervous system, called SLIC, for synthetic lethal in the central nervous system. Applying SLIC to the study of Huntington’s disease, we identify the age-regulated glutathione peroxidase 6 (Gpx6) gene as a modulator of mutant huntingtin toxicity and show that overexpression of Gpx6 can dramatically alleviate both behavioral and molecular phenotypes associated with a mouse model of Huntington’s disease. SLIC can, in principle, be used in the study of any neurodegenerative disease for which a mouse model exists, promising to reveal modulators of neurodegenerative disease in an unbiased fashion, akin to screens in simpler model organisms.

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