scholarly journals Artificial miRNAs Reduce Human Mutant Huntingtin Throughout the Striatum in a Transgenic Sheep Model of Huntington's Disease

2018 ◽  
Vol 29 (6) ◽  
pp. 663-673 ◽  
Author(s):  
Edith L. Pfister ◽  
Natalie DiNardo ◽  
Erica Mondo ◽  
Florie Borel ◽  
Faith Conroy ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mutant Huntingtin ◽  
Sheep Model ◽  
Transgenic Sheep

scholarly journals DNA methylation study of Huntington’s disease and motor progression in patients and in animal models

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ake T. Lu ◽  
Pritika Narayan ◽  
Matthew J. Grant ◽  
Peter Langfelder ◽  
Nan Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Genetic Disorder ◽  
Mammalian Species ◽  
Motor Score ◽  
Sheep Model ◽  
Mutation Status ◽  
Clinical Assessments ◽  
Transgenic Sheep

Abstract Although Huntington’s disease (HD) is a well studied Mendelian genetic disorder, less is known about its associated epigenetic changes. Here, we characterize DNA methylation levels in six different tissues from 3 species: a mouse huntingtin (Htt) gene knock-in model, a transgenic HTT sheep model, and humans. Our epigenome-wide association study (EWAS) of human blood reveals that HD mutation status is significantly (p < 10−7) associated with 33 CpG sites, including the HTT gene (p = 6.5 × 10−26). These Htt/HTT associations were replicated in the Q175 Htt knock-in mouse model (p = 6.0 × 10−8) and in the transgenic sheep model (p = 2.4 × 10−88). We define a measure of HD motor score progression among manifest HD cases based on multiple clinical assessments. EWAS of motor progression in manifest HD cases exhibits significant (p < 10−7) associations with methylation levels at three loci: near PEX14 (p = 9.3 × 10−9), GRIK4 (p = 3.0 × 10−8), and COX4I2 (p = 6.5 × 10−8). We conclude that HD is accompanied by profound changes of DNA methylation levels in three mammalian species.

Further Molecular Characterisation of the OVT73 Transgenic Sheep Model of Huntington's Disease Identifies Cortical Aggregates

2013 ◽  
Vol 2 (3) ◽  
pp. 279-295 ◽  
Author(s):  
◽  
Suzanne J. Reid ◽  
Stefano Patassini ◽  
Renée R. Handley ◽  
Skye R. Rudiger ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Molecular Characterisation ◽  
Sheep Model ◽  
Transgenic Sheep

scholarly journals Metabolic disruption identified in the Huntington’s disease transgenic sheep model

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Renee. R. Handley ◽  
Suzanne J. Reid ◽  
Stefano Patassini ◽  
Skye R. Rudiger ◽  
Vladimir Obolonkin ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Sheep Model ◽  
Transgenic Sheep ◽  
Metabolic Disruption

scholarly journals Identification of Full-Length Wild-Type and Mutant Huntingtin Interacting Proteins by Crosslinking Immunoprecipitation in Mice Brain Cortex

2021 ◽  
pp. 1-13
Author(s):  
Karen A. Sap ◽  
Arzu Tugce Guler ◽  
Aleksandra Bury ◽  
Dick Dekkers ◽  
Jeroen A.A. Demmers ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Brain Cortex ◽  
Full Length ◽  
Biological Processes ◽  
Interacting Proteins ◽  
Mutant Huntingtin ◽  
Wild Type ◽  
Mutant Huntingtin Protein ◽  
Mice Brain

Background: Huntington’s disease is a neurodegenerative disorder caused by a CAG expansion in the huntingtin gene, resulting in a polyglutamine expansion in the ubiquitously expressed mutant huntingtin protein. Objective: Here we set out to identify proteins interacting with the full-length wild-type and mutant huntingtin protein in the mice cortex brain region to understand affected biological processes in Huntington’s disease pathology. Methods: Full-length huntingtin with 20 and 140 polyQ repeats were formaldehyde-crosslinked and isolated via their N-terminal Flag-tag from 2-month-old mice brain cortex. Interacting proteins were identified and quantified by label-free liquid chromatography-mass spectrometry (LC-MS/MS). Results: We identified 30 interactors specific for wild-type huntingtin, 14 interactors specific for mutant huntingtin and 14 shared interactors that interacted with both wild-type and mutant huntingtin, including known interactors such as F8a1/Hap40. Syt1, Ykt6, and Snap47, involved in vesicle transport and exocytosis, were among the proteins that interacted specifically with wild-type huntingtin. Various other proteins involved in energy metabolism and mitochondria were also found to associate predominantly with wild-type huntingtin, whereas mutant huntingtin interacted with proteins involved in translation including Mapk3, Eif3h and Eef1a2. Conclusion: Here we identified both shared and specific interactors of wild-type and mutant huntingtin, which are involved in different biological processes including exocytosis, vesicle transport, translation and metabolism. These findings contribute to the understanding of the roles that wild-type and mutant huntingtin play in a variety of cellular processes both in healthy conditions and Huntington’s disease pathology.

scholarly journals Embryonic Mutant Huntingtin Aggregate Formation in Mouse Models of Huntington’s Disease

2016 ◽  
Vol 5 (4) ◽  
pp. 343-346 ◽  
Author(s):  
Alexander P. Osmand ◽  
Terry Jo. Bichell ◽  
Aaron B. Bowman ◽  
Gillian P. Bates
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mouse Models ◽  
Mutant Huntingtin ◽  
Aggregate Formation

scholarly journals Msh2 Acts in Medium-Spiny Striatal Neurons as an Enhancer of CAG Instability and Mutant Huntingtin Phenotypes in Huntington’s Disease Knock-In Mice

PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e44273 ◽  
Author(s):  
Marina Kovalenko ◽  
Ella Dragileva ◽  
Jason St. Claire ◽  
Tammy Gillis ◽  
Jolene R. Guide ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mutant Huntingtin ◽  
Striatal Neurons

scholarly journals Mutant huntingtin induces iron overload via up-regulating IRP1 in Huntington’s disease

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Li Niu ◽  
Cuifang Ye ◽  
Yun Sun ◽  
Ting Peng ◽  
Shiming Yang ◽  
...  
Keyword(s):  
Iron Overload ◽  
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
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