• Parkinson’s disease (PD) is a complex age-related neurodegenerative disease associated with dopamine deficiency and both motor and nonmotor deficits. The presence of alpha-synuclein positive cytoplasmic inclusions, termed Lewy bodies, in surviving neurons is one of the main hallmark of PD.
• The full coding sequences of human SNCA with A53T mutation including the 3’UTR that is driven by mouse Thy1 promoter are inserted into mouse Hipp11 (H11) locus in B-Thy1-hSNCA*A53T mice.
• Human SNCA mRNA was only detectable in B-Thy1-hSNCA*A53T mice. SNCA protein was only detectable in brain from B-Thy1-hSNCA*A53T mice.
• This model is suitable for drug screening applications, such as knockdown screening for small nucleic acids, but is not intended for efficacy studies.

Gene targeting strategy for B-Thy1-hSNCA*A53T mice. The full coding sequences of human SNCA with A53T mutation including the 3’UTR that is driven by mouse Thy1 promoter are inserted into mouse Hipp11 (H11) locus in B-Thy1-hSNCA*A53T mice.

Species specific analysis of SNCA gene expression in heterozygous B-Thy1-hSNCA*A53T mice. Striatum, midbrain, hippocampus and cortex were collected from heterozygous B-Thy1-hSNCA*A53T mice (H/+) (male, n=3, 6-7-week-old). As the human SNCA expression cassette was inserted into mouse Hipp11 (H11) locus in B-Thy1-hSNCA*A53T mice, the expression level of mouse and human SNCA could be detected at the same mice. The mRNA expression pattern of human SNCA in heterozygous B-Thy1-hSNCA*A53T mice was similar to those in the wild-type C57BL/6JNifdc mice. Values are expressed as mean ± SEM.

Western blot analysis of SNCA protein expression in heterozygous B-Thy1-hSNCA*A53T mice. Various tissue lysates were collected from C57BL/6JNifdc wild-type (+/+) mice and heterozygous B-Thy1-hSNCA *A53T mice (H/+), and then analyzed by western blot with human-specific anti-SNCA antibody (abcam, ab138501). 40 μg total proteins were loaded for western blotting analysis. SNCA was only detected in hippocampus, cortex from heterozygous B-Thy1-hSNCA*A53T mice, but not from wild-type mice.