Sv2c-KO Mouse

SV2C, a member of the synaptic vesicle glycoprotein 2 (SV2) family, is a synaptic vesicle protein involved in synaptic function. It has roles in vesicle trafficking, calcium-induced exocytosis, and synaptotagmin function, and is associated with regulating dopamine release. SV2C is also a receptor for botulinum neurotoxin/A [5,7].

Genetic deletion of SV2C in mice leads to reduced dopamine release in the dorsal striatum, decreased striatal dopamine content, disrupted α-synuclein expression, motor function deficits, and altered neurochemical effects of nicotine. In human studies, the SV2C rs1423099 single-nucleotide polymorphism is associated with sporadic Parkinson's disease (PD), especially in males. Other rare coding variants in SV2C, except p.Asp543Asn, do not seem to play a major role in PD susceptibility in East Asia. Additionally, miR-96 negatively regulates SV2C expression, leading to depression-like behavior and memory impairment in mice. A fiber-deprived diet causes cognitive impairment and reduces SV2C levels in mice, while lead exposure inhibits SV2C expression through NRSF [1,2,3,4,6,8].

In conclusion, SV2C is crucial for synaptic function, especially in dopamine-related processes. Mouse models with SV2C gene knockout have revealed its role in motor function and dopamine regulation, which is relevant to Parkinson's disease. The study of SV2C in various models helps in understanding its functions in normal and disease-related biological processes.

References:

1. Tan, Zixin, Lin, Yuwan, Zhou, Miaomiao, Xu, Pingyi, Chen, Xiang. 2023. Correlation of SV2C rs1423099 single nucleotide polymorphism with sporadic Parkinson's disease in Han population in Southern China. In Neuroscience letters, 813, 137426. doi:10.1016/j.neulet.2023.137426. https://pubmed.ncbi.nlm.nih.gov/37544580/

2. Chang, Chu Hua, Chew, Elaine Guo Yan, Lian, Michelle Mulan, Tan, Eng-King, Foo, Jia Nee. 2025. Rare SV2C coding variants in Parkinson's disease risk. In Journal of Parkinson's disease, 15, 66-71. doi:10.1177/1877718X241300298. https://pubmed.ncbi.nlm.nih.gov/39973496/

3. Sun, Lidong, Bai, Donghao, Lin, Maoguang, Wang, Fengzhen, Jin, Shangwu. 2021. miR-96 Inhibits SV2C to Promote Depression-Like Behavior and Memory Disorders in Mice. In Frontiers in behavioral neuroscience, 14, 575345. doi:10.3389/fnbeh.2020.575345. https://pubmed.ncbi.nlm.nih.gov/33815074/

4. Shi, Hongli, Ge, Xing, Ma, Xi, Huang, Xu-Feng, Yu, Yinghua. 2021. A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites. In Microbiome, 9, 223. doi:10.1186/s40168-021-01172-0. https://pubmed.ncbi.nlm.nih.gov/34758889/

5. Dunn, Amy R, Hoffman, Carlie A, Stout, Kristen A, Dhamsania, Rohan K, Miller, Gary W. 2017. Immunochemical analysis of the expression of SV2C in mouse, macaque and human brain. In Brain research, 1702, 85-95. doi:10.1016/j.brainres.2017.12.029. https://pubmed.ncbi.nlm.nih.gov/29274878/

6. Yang, Meiyuan, Li, Yaobin, Hu, Lei, Zhang, Lixia, Zhu, Gaochun. 2018. Lead exposure inhibits expression of SV2C through NRSF. In Toxicology, 398-399, 23-30. doi:10.1016/j.tox.2018.02.009. https://pubmed.ncbi.nlm.nih.gov/29505838/

7. Hu, Yan-Wei, Xiao, Lei, Zheng, Lei, Wang, Qian. 2017. Synaptic vesicle 2C and its synaptic-related function. In Clinica chimica acta; international journal of clinical chemistry, 472, 112-117. doi:10.1016/j.cca.2017.07.029. https://pubmed.ncbi.nlm.nih.gov/28774501/

8. Dunn, Amy R, Stout, Kristen A, Ozawa, Minagi, Caudle, W Michael, Miller, Gary W. 2017. Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease. In Proceedings of the National Academy of Sciences of the United States of America, 114, E2253-E2262. doi:10.1073/pnas.1616892114. https://pubmed.ncbi.nlm.nih.gov/28246328/