Endogenous synuclein | | | | |
Tg (sncga:GFP) | Tg (sncga:GFP) | Embryos | Transgenic GFP expression at 3 dpf in spinal cord, habenula, hindbrain, midbrain, eyes, trigeminal ganglion, vagal ganglion, and posterior lateral line ganglion. Habenula expression is asymmetric, larger GFP domain in left habenula than in right habenula. | Chen et al., 2009b |
β-synuclein (sncb) | MO knockdown | Embryos, larvae | Slight reduction in slc6a3 (dopamine transporter, dat)-positive neurons in double β + γ1 morphants at 2 dpf. Hypokinesia between 3–5 dpf, reduced dopamine levels at 7 dpf. Hypokinesia rescued by human human α-synuclein. | Milanese et al., 2012 |
γ-1 synuclein (sncga) | (β MO, γ1 MO, β + γ1 MO) |
β-synuclein | lrrk2 MO knockdown | Embryos | β-synuclein aggregation in lrrk2 morphant brain at 3 dpf. | Prabhudesai et al., 2016 |
γ-1 synuclein (sncga) | γ-1 synuclein MO | Embryos | Morphants protected from ziram dithiocarbamate toxicity. | Lulla et al., 2016 |
γ-1 synuclein (sncga) | γ1-synuclein overexpression in neurons via HuC-ZFγ1-T2A-DsRed injection at single-cell stage | Embryos | Malformation, reduced survival, intracytoplasmic aggregation in neurons at 2 dpf. | Lulla et al., 2016 |
α-synuclein (presumably sncb or sncga) | Rotenone (5 μg/L) immersion for 28 days | Adults | Western Blot detection of α-synuclein aggregates in the brain. Hypokinesia, decreased dopamine levels, increased apoptosis, increased α-synuclein, Caspase-3, Caspase-9 expression and decreased BDNF expression in midbrain. | Khotimah et al., 2015a; Khotimah et al., 2015b |
α-synuclein (presumably other synuclein ortholog) | Environmental toxins | Larvae, adults | Increased α-synuclein in embryos exposed to titanium dioxide nanoparticles.PD-like symptoms in zebrafish larvae but no increase in α-synuclein exposed to Fenvalerate type II pyrethroids.Increased α-synuclein in adults exposed to benzo[a]pyrene. | Hu et al., 2017Zhu et al., 2020Das et al., 2020 |
Exogeneous α-synuclein transgene |
Human α-syn, SNCA (HuC-α-syn-T2A-dsRed) transgenic | SNCA fused with DsRed reporter gene with HuC neuronal promoter and T2A peptide inserted between SNCA and DsRed sequence. Transgene injected into embryos at one-cell stage. | Embryos | HuC promoter used to drive α-syn DsRed expression in neurons. Embryos have morphological deformities, marked increase in neuron apoptosis as early as 24 hpf, aggregated α-syn in DsRed-positive neurons. Almost all dead by 240 hpf. | Prabhudesai et al., 2012 |
Human α-synuclein, SNCA (aSyn-2A-GFP) transgenic | CREST3:Gal4:UAS:aSyn-2A-GFP transgene injected into wildtype embryos at one-cell stage | Embryos | CREST3 enhancer used to drive expression in peripheral sensory neurons. Most embryos morphologically normal. Human α-syn GFP expression in Rohon-Beard neurons. α-synuclein aggregation by 2 dpf, reduced mitochondrial transport in axons at 2 dpf, axonopathy (axon swelling, beading, fragmentation, degeneration) by 3 dpf. | O’Donnell et al., 2014 |
Human α-synuclein xenograft and human α-synuclein (α-syn) transgenic | Human recombinant α-synuclein protein injected into the cerebrospinal fluid (CSF) of 3-month-old AB wildtype and α-syn transgenic (Xenopus neural-specificbeta tubulin (NBT) promoter:human α-synuclein IRESGFP) fish | Adults | α-syn transgenic adults with very weak human α-synuclein expression and absence of α-synuclein inclusion bodies at 18-months-old.At 3 months-post-injection, robust accumulation of human α-synuclein and presence of α-synuclein inclusion bodies throughout the brain in 6-month-old α-syn transgenic fish but not in wildtype fish. | Matsui & Matsui, 2017 |
Human α-synuclein, SNCA (α-Syn) transgenic | Tg (UAS:hsa.SNCA-2A-nls-mCherry) zebrafish expressing human wildtype α-synuclein crossed with Tg (otpb:gal4) Gal4 driver zebrafish line to activate UAS enchancer | Larvae | Co-expression of human α-synuclein (mCherry reporter) in ventral diencephalic dopaminergic neurons at low levels to avoid neurodegeneration or neurobehavioral abnormalities, with fluorescent biosensors for cytoplasmic peroxide flux and glutathione oxidation detection. | Van Laar et al., 2020 |
Human α-synuclein, SNCA (α-synuclein-GFP; A53T α-synuclein-GFP; S129A α-synuclein-GFP; S129D α-synuclein-GFP) transgenics | Human α-synuclein tagged with C-terminal Green Fluorescent Protein (α-synuclein-GFP) and zebrafish neuroD promoter. Transgeneinjected into AB/TL wildtype embryos at one-cell stage | Larvae | Human α-synuclein-GFP expression appearing at 2–4 dpf in the soma, axon, and presynaptic terminals of central and peripheral nervous system neurons, including some motor neurons projecting from the spinal cord. Robust expression persisting and neurons appeared healthy until at least 8 dpf. α-synuclein-GFP enriched in presynaptic terminals of neurons at 4 dpf for fluorescence recovery after photobleaching (FRAP) imaging detection of freely diffusing, synaptic vesicle-bound, and aggregated α-synuclein; and immunohistochemistry detection of phosphorylated α-synuclein. | Weston et al., 2021 |