Syn2-KO Mouse

Syn2, also known as synapsin II, is a neuron-specific phosphoprotein encoded by the SYN2 gene. It belongs to the synapsin multigene family (SYN1-3) and is involved in regulating neurotransmitter release and synaptogenesis [2]. Synapsins I and II, the major Syn isoforms in the adult brain, have partially overlapping functions and are implicated in synaptic function [2].

Nonsense and missense mutations in SYN2 are associated with autism spectrum disorders (ASDs) in humans, specifically in males. When expressed in SYN2 knockout neurons, wild-type human Syn II fully rescues the SYN2 knockout phenotype, while the nonsense mutant is not expressed and the missense mutants are virtually unable to modify the SYN2 knockout phenotype. This suggests that SYN2 is a novel predisposing gene for ASD, strengthening the hypothesis that synaptic homeostasis disturbance underlies ASD [2]. Polymorphisms of SYN2 also show significant associations with schizophrenia in the Korean population through haplotype analyses, indicating that SYN2 may confer susceptibility to schizophrenia [4]. Additionally, the SYN2-PPARG fusion has been found in small cell lung cancer, acinic cell carcinoma, and sinonasal adenocarcinoma, highlighting the molecular heterogeneity within these cancers and potentially aiding in specific therapy selection [1,3,5].

In conclusion, Syn2 plays a crucial role in synaptic function. Studies using gene knockout models have revealed its significance in neurodevelopmental disorders like ASD and schizophrenia. The discovery of SYN2-PPARG fusion in various cancers emphasizes its potential as a biomarker for targeted cancer therapies. These findings enhance our understanding of the biological functions of Syn2 and its implications in disease mechanisms.

References:

1. Ghigna, M R, Cotteret, S, Arbab, A, Bani, M A, Scoazec, J Y. 2023. Small cell lung cancer with SYN2::PPARG fusion. In Pathology, research and practice, 251, 154904. doi:10.1016/j.prp.2023.154904. https://pubmed.ncbi.nlm.nih.gov/38238071/

2. Corradi, Anna, Fadda, Manuela, Piton, Amélie, Benfenati, Fabio, Cossette, Patrick. 2013. SYN2 is an autism predisposing gene: loss-of-function mutations alter synaptic vesicle cycling and axon outgrowth. In Human molecular genetics, 23, 90-103. doi:10.1093/hmg/ddt401. https://pubmed.ncbi.nlm.nih.gov/23956174/

3. Dimbleby, Grace, Rettino, Alessandro, Jogai, Sanjay, Battison, Sobana, Moutasim, Karwan. 2024. A Case of Acinic Cell Carcinoma with SYN2::PPARG Fusion. In Head and neck pathology, 18, 107. doi:10.1007/s12105-024-01715-5. https://pubmed.ncbi.nlm.nih.gov/39417931/

4. Lee, Hee Jae, Song, Ji Young, Kim, Jong Woo, Shibata, Hiroki, Fukumaki, Yasuyuki. 2005. Association study of polymorphisms in synaptic vesicle-associated genes, SYN2 and CPLX2, with schizophrenia. In Behavioral and brain functions : BBF, 1, 15. doi:. https://pubmed.ncbi.nlm.nih.gov/16131404/

5. Soon, Gwyneth Shook Ting, Chang, Kenneth Tou En, Kuick, Chik Hong, Petersson, Fredrik. 2019. A case of nasal low-grade non-intestinal-type adenocarcinoma with aberrant CDX2 expression and a novel SYN2-PPARG gene fusion in a 13-year-old girl. In Virchows Archiv : an international journal of pathology, 474, 619-623. doi:10.1007/s00428-019-02524-w. https://pubmed.ncbi.nlm.nih.gov/30666415/