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Master of Science (MS)
Carroll, Jeffrey B. (Jeffrey Bryan), 1977-
Huntington’s disease (HD) is a progressive, fatal neurodegenerative disease caused by an inherited CAG expansion on the Huntingtin (HTT) gene resulting in cognitive, affective, and motor related symptoms. Although clinical diagnosis depends on the presence of Huntington’s chorea, a movement disorder consisting of irregular movements, cognitive symptoms appear 10-15 years prior during the pre-manifest stage of the disease and are more debilitating to patients. One of the most important advances in HD research has been the generation of mouse models that recapitulate the features of human HD, allowing researchers to identify the pathogenic mechanisms associated with the disease and test the potential therapeutic treatments. Unfortunately, many treatments that have been successful in mouse models have failed to translate to humans when tested in pre-clinical trials. This is partly because experimenters have largely focused on improving late-stage features of HD such as cell death and motor dysfunction, and utilized transgenic mouse that are severely impaired but poorly reproduce the pathogenic processes that underlie the disease. In contrast, knock-in (KI) mouse models are genetically faithful to the human condition but remain underutilized in pre-clinical research due to their slower progression and subtle overt phenotype. This thesis characterized the behavioral deficits associated with the HttQ111/+ KI mouse model of HD and discovered novel cognitive phenotypes that are characteristic of the pre-manifest stage of the disease. At nine months of age, HttQ111/+ mice display improved procedural memory on the two-cue MWM, hypoactivity, reduced velocity, and increased anxiety during open field exploration, and intact spatial LTM with a reduction in the total number of investigations toward both objects during an object location task. Together, these tasks provide a number of robust behavioral phenotypes for use in pre-clinical research conducted in the HttQ111/+ mouse model of HD in the future.
Western Washington University
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Minnig, Shawn, "Behavioral Characterization of a Knock-in Mouse Model of Huntington's Disease" (2016). WWU Masters Thesis Collection. 479.