Table 1 Comparison of various VPS35 animal models studies
From: Altered striatal dopamine levels in Parkinson’s disease VPS35 D620N mutant transgenic aged mice
Paper | Impaired striatal dopamine release in homozygous Vps35 D620N knock-in mice (Ishizu et al. 2016) | Altered dopamine release and monoamine transporters in Vps35 p.D620N knock-in mice (Cataldi et al. 2018) | Parkinson’s disease-linked D620N VPS35 knockin mice manifest tau neuropathology and dopaminergic neurodegeneration (Chen et al. 2019) | Parkinson’s disease-linked mutations in VPS35 induce dopaminergic neurodegeneration (Tsika et al. 2014) | Parkinson’s disease genes VPS35 and EIF4G1 interact genetically and converge on α-synuclein (Dhungel et al. 2015) | Our study | |
|---|---|---|---|---|---|---|---|
Age | Aged, 17.5 months VPS35 and VPS35 D620N mice | Adult VPS35 and VPS D620N mice | Adult and aged, 3–24 months VPS35 and VPS35 D620N mice | VPS35 and VPS35 D620N virus injected into adult wildtype rat | VPS35 virus injected into adult α-synuclein mice | Aged, 20 months VPS35 D620N mice | |
Sex | Male and female | Male | Male and female | N.A | N.A | Male and female | |
Generation | Mouse (KI) | Mouse (KI) | Mouse (KI) | Virus injected rat | Virus injected mouse | Mouse (Tg) | |
Biochemistry results | Western blot | No change in DRP1, LC3-II, Cathepsin D, Tom20, VDAC1, MUL1, α-synuclein, Parkin, LAMP1, GM130, and EEA1 | No change in TH ↑ VMAT2 ↓ DAT in VPS35 D620NfemaleKI mice | No change in VPS35 and α-synuclein | No change in VPS35, Sortilin, SorLA, Cathepsin D, and TH in VPS35 and VPS35 D620N virus injected rats | N. A | No change in Drp1, LC3-II, Tom20, TH, DD2R, DAT, Mfn2, α-synuclein, and AT8 in VPS35 D620N Tg mice |
Immuno-histochemical staining | N.A | ↓ DAT integrated density ↓ DAT area in VPS35 D620N KI mice | ↑ AT8 ↑ Tau5 ↑ MT1 ↑ APP + spheroids ↑ degenerating neuritic processes in VPS35 D620N KI mice | ↑ TUNEL assay = ↑ neuronal cell death ↓ neurite outgrowth ↑ neuronal vulnerability to cellular stress in VPS35 and VPS35 D620N virus injected rats | ↑ NeuN ↓ α-synuclein ↓ GFAP ↓ neuroinflammation in VPS35 virus injected α-synuclein mice | N. A | |
HPLC | No change in DA, DOPAC, and HVA | No change in DA, DOPAC, and HVA ↑ (DOPAC + HVA)/DA ratio in VPS35 D620N | No change in DA, DOPAC, and HVA | N.A | N.A | ↑ DA in VPS35 D620N Tg No change in DOPAC, HVA, and (DOPAC + HVA)/DA ratio | |
Stereological analysis of TH + neurons | No significant difference observed | No significant difference observed | ↓ in VPS35 D620N KI mice | ↓ in VPS35 D620N injected rats | N.A | No significant difference observed | |
Behavior results | Open-field test: no difference | Open-field, rotarod, and cylinder test: no difference | Open-field, rotarod, and gait analyses: no difference | Cylinder test: no difference between control, VPS35, and VPS35 D620N | N.A | Open-field, rotarod, and elevated plus maze: no difference | |