Table 3.
AD toxicity models of human proteins expressed in C. elegans
| Human protein/peptide | C. elegans promoter | Expression in C. elegans | Phenotypes | Strain/transgene name/(plasmid) | References |
|---|---|---|---|---|---|
| Expression of the human beta amyloid peptide | |||||
| Aβ1-42 (wild type) | unc-54 | constitutively in muscles | age-dependent progressive paralysis; forms amyloid deposits; increased oxidative stress | CL2005, CL2006, CL1019, CL1118, CL1119, CL1120, CL1121, CL2120 | (Fay et al. 1998; Link 1995; Link et al. 2001; Yatin et al. 1999) |
| Dimer Aβ1-42 | no formation of amyloid deposits | CL2109, CL3109 | (Fay et al. 1998; Link et al. 2001) | ||
| Met35Cys Aβ1-42 | no formation of amyloid deposits; no increase in oxidative stress | CL3115 | (Fay et al. 1998; Yatin et al. 1999) | ||
| Aβ1-42 (with long 3′UTR) | myo-3 | inducible Aβ1-42 in body wall muscles | rapid paralysis; oxidative stress precedes amyloid deposition; autophagosome accumulation | CL4176 | (Drake et al. 2003; Florez-McClure et al. 2007; Link et al. 2003) |
| Aβ1-42 | snb-1 | inducible Aβ1-42 in all neurons | normal movement; forms amyloid deposits; reduced chemotaxis towards Benzaldehyde; hypersensitive to serotonin | CL2241, CL2355 | (Link 2006; Wu et al. 2006) |
| Expression of Components of the γ-Secretase Complex | |||||
| PSEN1 | sel-12 | constitutively in most cell types, except intestine | rescues sel-12 null phenotypes | PS1, (pBY146) | (Levitan et al. 1996; Wittenburg et al. 2000) |
| Mutant PSEN1 variants | fails to rescue sel-12 null phenotypes | PS1ΔE9, PS1M146L, PS1H163R, PS1L266V, PS1A286E, PS1C410Y, A246(pBY147) | (Levitan et al. 1996; Wittenburg et al. 2000) | ||
| PSEN2 | rescues sel-12 null phenotypes | PS2 | (Levitan et al. 1996) | ||
| Nicastrin | rescues egg-laying defect of aph-2 null | hNCT FL | (Levitan et al. 2001) | ||
| Mutant Nicastrin variants | partially rescues egg-laying defect of aph-2 null | DYIGS, AAIGS, Δ340, Δ 69, EC | (Levitan et al. 2001) | ||
| APH-1 | human APH-1 is unable to rescue egg-laying defect of aph-1 null worms; human APH-1 can partially rescue egg-laying defect of aph-1 null only in mixture with Hpen-2, Haph-1a, Haph1b and HPSEN1 | Haph-1a, Haph1b | (Francis et al. 2002) | ||
| PEN-2 | Partially rescues egg-laying defect of pen-2 null (with long 3′ UTR) only in mixture with Hpen-2, Haph-1a, Haph1b and HPSEN1 | Hpen-2 | (Francis et al. 2002) | ||
| Expression of Human Tau and Variants | |||||
| Tau (4R1N isoform, most abundant form in human brain) | aex-3 | constitutively in all neurons | age-dependent progressive uncoordination and accumulation of insoluble tau; neurodegeneration; reduced lifespan compared to non- transgenic worms | N-1, N-2 | (Kraemer et al. 2003) |
| V337M Tau (4R1N) (FTDP-17 mutation) | aex-3 | constitutively in all neurons | stronger age-dependent progressive uncoordination and accumulation of insoluble tau; neurodegeneration; reduced lifespan compared to non-transgenic worms | 337M-1,3337M-2 | (Kraemer et al. 2003) |
| P301L tau (4R1N) (FTDP-17 mutation) | aex-3 | constitutively in all neurons | strong age-dependent progressive uncoordination and accumulation of insoluble tau; neurodegeneration; reduced lifespan compared to non-transgenic worms | 301L-1, 301L-2 | (Kraemer et al. 2003) |
| Tau WT4R (wild type) | mec-7 | touch neurons (ALML/R, AVM, PLML/R, PVM); weak in FLP, PVD, BDU | age-dependent progressive impairment in touch response; neurodegeneration; little tau accumulation in PLM neuron | tmIs82, tmIs83, tmIs84, tmIs85, tmIs171 | (Miyasaka et al. 2005) |
| Tau WT R (wild type) | mec-7 | touch neurons (ALML/R, AVM, PLML/R, PVM); weak in FLP, PVD, BDU | age-dependent progressive impairment in touch response, neurodegeneration | tmIs110, tmIs173 | (Miyasaka et al. 2005) |
| P301L tau (FTDP-17 mutation) | mec-7 | touch neurons (ALML/R, AVM, PLML/R, PVM); weak in FLP, PVD, BDU | strong age-dependent progressive impairment in touch response; neurodegeneration; strong tau accumulation in PLM neuron (as wild type tau WT4R) | tmIs81, tmIs178, tmIs179 | (Miyasaka et al. 2005) |
| R406W tau (FTDP-17 mutation) | mec-7 | touch neurons (ALML/R, AVM, PLML/R, PVM); weak in FLP, PVD, BDU | strong age-dependent progressive impairment in touch response; neurodegeneration; strong tau accumulation in PLM neuron (as wild-type tau WT4R) | tmIs146, tmIs147, tmIs148, tmIs149 | (Miyasaka et al. 2005) |
| Tau352 (=fetal, 352aa isoform) wildtype | rgef-1 | constitutively in all neurons | age-dependent progressive uncoordination; neurodegeneration | VH255, VH1016, VH1018 | (Brandt et al. 2009) |
| Tau352 PHP (pseudo- hyperphosphorylated) | rgef-1 | constitutively inall neurons | strong-age dependent progressive uncoordination; neurodegeneration | VH254, VH1014, VH1015, | (Brandt et al. 2009) |
| Tau352 Ala (10 Ser/Thr phosphorlyation sites substituted with Ala) | rgef-1 | constitutively in all neurons | early onset of age-dependent progressive uncoordination and reduced lifespan compared towild- type tau352 | VH418, VH421 | (Brandt et al. 2009) |