TABLE 2.

Models of Aberrant Developmentally Important Proteins Purported to Be of Relevance for Parkinson’s Disease

Gene Product	Inheritance Pattern in Human Disease	Type of Model	Characterization
α-Synuclein	Dominant point mutations; Parkinson’s disease	Knock-out mice; mutation, mice; cultured dopaminergic mesencephalic cells overexpressing wild-type or mutant	Knock-out mice: reduction in striatal dopamine and an attenuation of dopamine-dependent locomotor response to amphetamine, resistance to MPTP; overexpressing cells: death of dopaminergic neurons; mutant α-synuclein controlled by a prion promoter in mice: Lewy bodies in dopaminergic neurons
Parkin	Recessive; parkinsonian syndrome	Mutation, mice	Mutant mice: deficits in glutamate transmission, late-onset hypokinetic motor deficits; cultured cells from mutant mice: resistance of mesencephalic cells to nitric oxide toxicity
UCH-L1	Dominant; polymorphism putatively inversely correlated with Parkinson’s disease	Mutation, mice	Isolated mutant UCH-L1 mice: sensory ataxia, posterior paralysis, death; overexpression of α-synuclein in UCH-L1 mutant mice: accelerated dopaminergic neuron loss in mesencephalon relative to overexpression of α-synuclein in UCH-L1 wild-type mice
PINK1	Recessive; parkinsonian syndrome	Heterozygous deletion, Drosophila; conditional knock-out, mice	Drosophila: progressive loss of dopaminergic neurons and retinal neurons preventable with antioxidants; mice: decreases in evoked striatal slice dopamine release, reductions in dissociated chromaffin cell catecholamine quantal size and release frequency
DJ-1	Recessive; parkinsonian syndrome	Mutant, Drosophila; deficiency, mice	Hypersensitivity to MPTP and oxidative stress
LRRK2	Dominant; Parkinson’s disease	Mutant, Drosophila; mutant and knock-out mice	Loss of dopaminergic neurons in Drosophila; age-dependent and L-dopa–responsive hypokinesia, diminished dopamine release, nigrostriatal dopaminergic projection axonal pathology with Lewy bodies in mice

MPTP = 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; UCH-L1 = ubiquitin C-terminal hydrolase L1; PINK1 = PTEN-induced kinase 1; LRRK2 = leucine-rich repeat kinase 2.