Mouse Models of Polyglutamine Diseases: Review and Data Table. Part I

Abstract

Polyglutamine (polyQ) disorders share many similarities, such as a common mutation type in unrelated human causative genes, neurological character, and certain aspects of pathogenesis, including morphological and physiological neuronal alterations. The similarities in pathogenesis have been confirmed by findings that some experimental in vivo therapy approaches are effective in multiple models of polyQ disorders. Additionally, mouse models of polyQ diseases are often highly similar between diseases with respect to behavior and the features of the disease. The common features shared by polyQ mouse models may facilitate the investigation of polyQ disorders and may help researchers explore the mechanisms of these diseases in a broader context. To provide this context and to promote the understanding of polyQ disorders, we have collected and analyzed research data about the characterization and treatment of mouse models of polyQ diseases and organized them into two complementary Excel data tables. The data table that is presented in this review (Part I) covers the behavioral, molecular, cellular, and anatomic characteristics of polyQ mice and contains the most current knowledge about polyQ mouse models. The structure of this data table is designed in such a way that it can be filtered to allow for the immediate retrieval of the data corresponding to a single mouse model or to compare the shared and unique aspects of many polyQ models. The second data table, which is presented in another publication (Part II), covers therapeutic research in mouse models by summarizing all of the therapeutic strategies employed in the treatment of polyQ disorders, phenotypes that are used to examine the effects of the therapy, and therapeutic outcomes.Electronic supplementary materialThe online version of this article (doi:10.1007/s12035-012-8315-4) contains supplementary material, which is available to authorized users.

The Role for Alterations in Neuronal Activity in the Pathogenesis of Polyglutamine Repeat Disorders

“…For the sake of clarity, the research that has been done examining dysfunction in each of these cell types is presented separately, and special attention is paid to establishing the timing of these changes and their relationship to the development of symptoms. This work has been derived primarily from 3 of the many rodent models of HD (reviewed in [55]), namely the R6/ 2 model, which expresses a fragment of the HTT gene containing the promoter, exon 1, and intron 1 [16]; the YAC128 model, which expresses full-length HTT within a yeast artificial chromosome [56]; and the HdhQ200 model, which contains a 200-repeat expansion of the endogenous CAG tract in the mouse Htt gene [57].…”

Prion-Like Characteristics of Polyglutamine-Containing Proteins

“…Expression of pathogenic polyQ proteins in yeast, worm, fly, and mouse models recapitulates many aspects of neurodegenerative disease, including cell death, mitochondrial dysfunction, impaired synaptic activity, reactive gliosis, and disrupted protein homeostasis (Mangiarini et al 1996; Scherzinger et al 1997; Klement et al 1998; Warrick et al 1998; Marsh et al 2000; Meriin et al 2002; Morley et al 2002; Yu et al 2003; Bennett et al 2007; Figiel et al 2012; Tsou et al 2015). These genetic models have been used in numerous screens to identify modifiers of polyQ disease toxicity.…”

Induced Pluripotent Stem Cells in Huntington’s Disease: Disease Modeling and the Potential for Cell-Based Therapy

“…Both chemically induced and transgenic animal models that recapitulate features of HD have enabled plenty of powerful avenues for research [47, 48]. However, traditional animal models may not be able to precisely mimic the disease process in human cells due to differences between species [49].…”