The B6-hSNCA (3'UTR) mouse is a humanized model constructed by replacing the mouse Snca gene in situ with the human SNCA gene, in which the sequences from ATG start codon to ~0.5 kb downstream of 3'UTR of the endogenous mouse Snca gene will be replaced with the sequences from ATG start codon to ~0.5 kb downstream of 3'UTR of the human SNCA gene. The homozygous B6-hSNCA (3'UTR) mice are viable and fertile and can be used for studies on Parkinson's disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA), and pathogenesis of neurodegenerative diseases, as well as for SNCA-targeted drug development.