TABLE 2.
Gene expression impairments in polyQ SCA mouse models.
| Disease | Mouse model name | Design | Mutant protein expression | Phenotypes and neuropathology | Deregulation of genes, pathways and epigenetic | References |
| SCA1 | SCA1[82Q] | Tg; Pcp-2 promoter, ATXN1 cDNA with 82 CAGs | PC; overexpress | Motor phenotype; cerebellar and PC pathology | LTD; Glutamate signaling in PC; Cell signal transduction; calcium homeostasis; multicellular impairments: PCP; IO: immune system, ISG | Lin et al., 2000; Serra et al., 2004; Ingram et al., 2016; Driessen et al., 2018 |
| Atxn1154Q/2Q | KI;154 CAGs in Atxn1 | Ubiquitous; endogenous level | Motor phenotype; cerebellar and PC pathology | PC: cellular signaling pathways; Igfbp5 and IGF pathway crosstalk PC-GC; medulla: metabolic pathways; IO: immune system; ISG; histone H3 hypoacetylation | Gatchel et al., 2008; Cvetanovic et al., 2012; Driessen et al., 2018 | |
| SCA2 | SCA2-127Q | Tg; Pcp-2 promoter, ATXN2 cDNA with 127 CAGs | PC; overexpress | Motor phenotype; cerebellar and PC pathology | LTD; phosphatidylinositol; calcium homeostasis; small GTPase-mediated signaling; mRNA transport; synaptogenesis; axon guidance | Hansen et al., 2013; Pflieger et al., 2017 |
| BAC-Q72 | Tg; BAC containing human ATXN2 with 72 CAGs | Brain; endogenous level; overexpress in PC and basal ganglia | Motor phenotype; cerebellar and PC pathology | Calcium homeostasis; Glutamate signaling; voltage-gated ion channel activity | Dansithong et al., 2015 | |
| Atxn2-CAG100 | KI; 100 CAGs in Atxn2 | Ubiquitous; endogenous level | Motor phenotype | Myelination | Sen et al., 2019a | |
| SCA3 | Ataxin-3-Q79 | Tg; Prion promoter, ATXN3 cDNA with 79 CAGs; | Whole brain except PC; overexpress | Motor phenotype; cerebellar and PC pathology | LTD; Glutamate signaling in PC; Cell signal transduction; calcium homeostasis; GABA receptors; gene expression regulators; histone H3 and H4 hypoacetylation | Chou et al., 2008 |
| YAC84Q (MJD84.2) | Tg; YAC containing ATXN3 with 76–77 CAGs | Ubiquitous; endogenous level | No motor phenotype | CREB signaling; cholesterol biosynthesis; myelination; striatum: axon guidance; neurotransmission brainstem: cell signaling; aa metabolism | Toonen et al., 2018 | |
| SCA3 | KI; 82 CAGs in Atxn3 | Ubiquitous; endogenous level | No motor phenotype | Myelination | Ramani et al., 2017 | |
| SCA6 | PCαACTSCA6 | Tg; Pcp-2 promoter, α1ACT cDNA with 33 CAGs | PC; overexpress | Weak motor phenotype; cerebellar and PC pathology | Neurite outgrowth; neuronal differentiation | Du et al., 2013 |
| SCA6-MPI118Q/118Q | KI; 118 CAGs in Cacna1a | Ubiquitous; endogenous level | Motor phenotype; cerebellar and PC pathology | GPCR signaling; Neuroinflammation | Aikawa et al., 2015 | |
| SCA7 | R7E | Tg; Rho promoter, ATXN7 cDNA with 90 CAGs | Rod photoreceptors; overexpress | Photoreceptor dysfunction and dystrophy | Phototransduction pathway; H3 hypoacetylation | Abou-Sleymane et al., 2006 |
| ataxin-7-Q52 | Tg; PDGF-B promoter, ATXN7 cDNA with 52 CAGs | Brain; overexpress | Motor phenotype; cerebellar and PC pathology | Myelination; synaptic transmission; signal transduction; axon transport; neuronal differentiation | Chou et al., 2010 | |
| PrP-SCA7-92Q | Tg; Prion promoter, ATXN7 cDNA with 92 CAGs | Whole brain except PC; overexpress | Photoreceptor dysfunction and dystrophy; Motor phenotype; cerebellar and PC pathology | Phototransduction pathway; H3 hypoacetylation | La Spada et al., 2001; Palhan et al., 2005 | |
| Gfa2-SCA7-92Q | Tg; Gfa2 promoter, ATXN7 cDNA with 92 CAGs | Bergmann glia | Motor phenotype; cerebellar and PC pathology | Glutamate transporter genes | Custer et al., 2006 | |
| mPrP-fx SCA7-92Q BAC | Tg; Prion promoter in BAC ATXN7 cDNA with 92 CAGs; eGFP | Whole brain; endogenous level | Motor phenotype; cerebellum and PC pathology | Phosphatidylinositol and calcium signaling | Stoyas et al., 2019 | |
| SCA7266Q/5Q | KI; 266 CAGs in Atxn7 | Ubiquitous; endogenous level | Photoreceptor dysfunction and dystrophy; motor phenotype; cerebellar and PC pathology | Phototransduction pathway; transcription factor; MHC class I; cell signaling; Igfbp5 and IGF pathway | Yoo et al., 2003; Gatchel et al., 2008 | |
| SCA17 | TBP-71Q/TBP-105Q | Tg; Prion promoter, TBP cDNA with 71 or 105 CAGs | Whole brain except PC; overexpress | Motor phenotype; cerebellar and PC pathology | Downregulation of Hspb1 and HSPA5 | Friedman et al., 2007; Huang et al., 2011 |
| TBP-105Q | KI; 105 CAGs in Tbp | Ubiquitous; endogenous level | Motor phenotype; cerebellar and PC pathology skeletal muscle phenotype | Synaptic transmission; calcium signaling; immune system; muscle specific genes | Yang et al., 2014; Huang S. et al., 2015; Liu et al., 2020 |
Tg, transgenic; KI, knockin; YAC, yeast artificial chromosome; BAC, bacterial artificial chromosome; PC, Purkinje cells; GC, granule cells; IO, inferior olive; GPCR, G-protein coupled receptor; PCP, planar cell polarity; ISG, interferon stimulated gene; aa, amino acid.