Table 2.
Model systems used to study UPS function in polyglutamine expansion disorders. See text for further details.
Model | Methods used in conjunction | Additional notes | Reference |
Human post mortem brain | Immunocytochemistry, assay of proteasome activity in lysates using fluorescent substrates | [3, 20, 30] | |
Human patient skin fibroblasts | Proteasome activity using fluorescent substrates | [30] | |
R6/2 transgenic mouse model of HD | Proteasome activity, immunocytochemistry, | R6/2 mouse generated by Mangiarini et al. [60] | [21, 34] |
R6/1 transgenic mouse model of HD | Proteasome activity | R6/1 mouse generated by Mangiarini et al. [60] | [15] |
HD94 conditional mouse model of HD | Chymotrypsin-like, trypsin-like or peptidyl-glutamyl activity in lysates | HD94 conditional mouse generated by Yamamoto et al. [61] | [33] |
SCA 7 knock-in mouse model | Crossed to a transgenic mouse expressing an EGFP–degron reporter | SCA 7 transgenic mouse generated by Yoo et al. [62] | [31] |
Transgenic Drosophila models of polyglutamine expansion disorders | Genetic screens | [56] | |
Cell models of HD and SCA, stable cell lines and transient expression of mutant constructs. Inducible or constitutive transgene expression | Immunocytochemistry, assay of proteasome activity in lysates using fluorescent substrates, co-expression of construct with fluorescent–degron reporter. | [13-15, 20, 29, 32] | |
C. elegans models | Co-expression of mutant ataxin-3 and a ubiquitin-conjugated dsRed reporter | [37] |