Longitudinal in vivo MRI in a Huntington's disease mouse model: Global atrophy in the absence of white matter microstructural damage.

Huntington's disease (HD) is a genetically-determined neurodegenerative disease. Characterising neuropathology in mouse models of HD is commonly restricted to cross-sectional ex vivo analyses, beset by tissue fixation issues. In vivo longitudinal magnetic resonance imaging (MRI) allows for disease progression to be probed non-invasively.

Comparison of mHTT Antibodies in Huntington's Disease Mouse Models Reveal Specific Binding Profiles and Steady-State Ubiquitin Levels with Disease Development.

Huntington's disease (HD) cellular pathology is characterised by the aggregation of mutant huntingtin (mHTT) protein into inclusion bodies. The present paper compared the sensitivity of five widely used mHTT antibodies (S830; MW8; EM48; 1C2; ubiquitin) against mice from five commonly used HD mouse models (R6/1; YAC128; HdhQ92; B6 HdhQ150; B6 x129/Ola HdhQ150) at two ages to determine: the most sensitive antibodies for each model; whether mHTT antibody binding differed depending on aggregation stage (diffuse versus frank inclusion); the role of ubiquitin during aggregation as the ubiquitin proteosome system has been implicated in disease development. The models demonstrated unique profiles of antibody binding even when the models varied only by background strain (HdhQ150).

Similar striatal gene expression profiles in the striatum of the YAC128 and HdhQ150 mouse models of Huntington's disease are not reflected in mutant Huntingtin inclusion prevalence.

Background: The YAC128 model of Huntington's disease (HD) shows substantial deficits in motor, learning and memory tasks and alterations in its transcriptional profile. We examined the changes in the transcriptional profile in the YAC128 mouse model of HD at 6, 12 and 18 months and compared these with those seen in other models and human HD caudate.

Results: Differential gene expression by genotype showed that genes related to neuronal function, projection outgrowth and cell adhesion were altered in expression.

Optimising Golgi-Cox staining for use with perfusion-fixed brain tissue validated in the zQ175 mouse model of Huntington's disease.

Background: The Golgi-Cox stain is an established method for characterising neuron cell morphology. The method highlights neurite processes of stained cells allowing the complexity of dendritic branching to be measured.

New Methods: Conventional rapid Golgi and Golgi-Cox methods all require fresh impregnation in unfixed brain blocks.

Profiles of motor and cognitive impairment in the transgenic rat model of Huntington's disease.

The transgenic Huntington's disease (tgHD) rat strain provides a well regarded transgenic animal model of Huntington's disease, offering the prospect for a more detailed functional analysis in rats, along with neurological and therapeutic interventions, than is possible in the more widely available mouse models. In the present experiments, we compare the performance of heterozygous and homozygous tgHD rats against wildtype littermates on a range of motor and cognitive assessments in five separate cohorts of rats between 8 and 22 months of age. Male but not female heterozygous tgHD rats exhibit modest motor deficits in rotarod and staircase reaching tests, whereas most cognitive tests (including object recognition, exploration of novelty, delayed alternation, choice reaction time, and serial implicit learning tasks) revealed at best small or inconsistent deficits, in homozygous as well as heterozygous animals, up to 22 months of age.

Light and electron microscopic characterization of the evolution of cellular pathology in the R6/1 Huntington's disease transgenic mice.

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expansion of CAG repeats in the Htt gene. Examination of the post-mortem brains of HD patients shows the presence of diffuse nuclear htt immunoreactivity and intra-nuclear inclusions. The aim of this study was to produce a detailed characterization of the neuronal pathology in the R6/1 transgenic mouse model.

Selective cognitive impairment in the YAC128 Huntington's disease mouse.

People with HD have a demonstrated early extra-dimensional set-shifting deficit. In the present study, we use a novel water T-maze set-shifting procedure and demonstrate its validity as a set-shifting task in a mouse model of Huntington's disease. Three groups of YAC128 mice of different ages (27, 69 and 117 weeks) were run on the task, which incorporated six distinct stages in which the mice must learn a rule and then switch to a different rule.

Light and electron microscopic characterization of the evolution of cellular pathology in YAC128 Huntington's disease transgenic mice.

Huntington's disease (HD) is a progressive neurodegenerative disease caused by the insertion of an expanded polyglutamine sequence within the huntingtin protein. This mutation induces the formation of abnormal protein fragment aggregations and intra-nuclear neuronal inclusions in the brain. The present study aimed to produce a detailed longitudinal characterization of the neuronal pathology in the YAC128 transgenic mouse brain, to determine the similarity of this mouse model to other mouse models and the human condition in the spatial and temporal deposition pattern of the mutant protein fragments.

Light and electron microscopic characterization of the evolution of cellular pathology in HdhQ92 Huntington's disease knock-in mice.

Huntington's disease (HD) is a fatally progressive neurodegenerative disease that is characterized anatomically by the abnormal accumulation of fragments of mutant huntingtin protein, within the glia and neurons of the brain. Several genetic (transgenic and knock-in) animal models have been established to mimic human HD. None of these models represent all of the elements of the human disease, but they provide an opportunity to understand the processes of the disease and aid in the development of therapeutic strategies.

Light and electron microscopic characterization of the evolution of cellular pathology in the Hdh(CAG)150 Huntington's disease knock-in mouse.

Huntington's disease is an autosomal dominant, progressive neurodegenerative disease in which a single mutation in the gene responsible for the protein huntingtin leads to a primarily striatal and cortical neuronal loss, resulting progressive motor, cognitive and psychiatric disability and ultimately death. The mutation induces an abnormal protein accumulation within cells, although the precise role of this accumulation in the disease process is unknown. Several animal models have been created to model the disease.