Vamp2-KO Mouse

VAMP2, also known as vesicle-associated membrane protein 2, is a key component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. It is involved in vesicular trafficking and membrane fusion processes, which are crucial for various biological functions such as neurotransmitter release, cell membrane expansion, and autophagy regulation [2,3,4,7]. These processes are fundamental to normal physiological function and are associated with pathways related to synaptic physiology, epidermal differentiation, and myelination. Genetic models, including KO/CKO mouse models, have been instrumental in understanding VAMP2's function.

In KO mouse models, deletion of VAMP2 leads to aberrant skin stratification and enucleation, highlighting its importance in murine epidermal differentiation and carcinogenesis [1]. In oligodendrocytes, genetic inactivation of VAMP2/3 causes severe hypomyelination and premature death, indicating its essential role in CNS myelination [2]. Toxin-mediated cleavage of VAMP2/3 in the OL lineage of mice impairs the maturation of early oligodendrocytes into myelinating ones [5]. In addition, VAMP2 mutations in patients result in global developmental delay, autistic tendencies, and epilepsy, and in cellular models, these mutations decrease exocytosis and the number of synaptic vesicles released from the recycling pool [6].

In conclusion, VAMP2 is essential for multiple biological processes, including epidermal differentiation, CNS myelination, and synaptic function. Studies using KO/CKO mouse models and human cellular models with VAMP2 mutations have revealed its significance in diseases related to skin development, neurodegeneration, and neurological disorders, providing insights into potential therapeutic strategies for these conditions.

References:

1. Liu, Han, Su, Peihong, Li, Yuanyuan, Tan, Minjia, Wu, Xiaoyang. 2024. VAMP2 controls murine epidermal differentiation and carcinogenesis by regulation of nucleophagy. In Developmental cell, 59, 2005-2016.e4. doi:10.1016/j.devcel.2024.05.004. https://pubmed.ncbi.nlm.nih.gov/38810653/

2. Lam, Mable, Takeo, Koji, Almeida, Rafael G, Kantarci, Husniye, Zuchero, J Bradley. 2022. CNS myelination requires VAMP2/3-mediated membrane expansion in oligodendrocytes. In Nature communications, 13, 5583. doi:10.1038/s41467-022-33200-4. https://pubmed.ncbi.nlm.nih.gov/36151203/

3. Abbineni, Prabhodh S, Briguglio, Joseph S, Chapman, Edwin R, Holz, Ronald W, Axelrod, Daniel. 2021. VAMP2 and synaptotagmin mobility in chromaffin granule membranes: implications for regulated exocytosis. In Molecular biology of the cell, 33, ar53. doi:10.1091/mbc.E21-10-0494. https://pubmed.ncbi.nlm.nih.gov/34851717/

4. Meijer, Marieke, Öttl, Miriam, Yang, Jie, Zhang, Yongli, Verhage, Matthijs. 2024. Tomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes. In Nature communications, 15, 2652. doi:10.1038/s41467-024-46828-1. https://pubmed.ncbi.nlm.nih.gov/38531902/

5. Fekete, Christopher D, Horning, Robert Z, Doron, Matan S, Nishiyama, Akiko. 2023. Cleavage of VAMP2/3 Affects Oligodendrocyte Lineage Development in the Developing Mouse Spinal Cord. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 43, 6592-6608. doi:10.1523/JNEUROSCI.2206-21.2023. https://pubmed.ncbi.nlm.nih.gov/37620160/

6. Simmons, Roxanne L, Li, Haiyan, Alten, Baris, Sherr, Elliott H, Voglmaier, Susan M. 2020. Overcoming presynaptic effects of VAMP2 mutations with 4-aminopyridine treatment. In Human mutation, 41, 1999-2011. doi:10.1002/humu.24109. https://pubmed.ncbi.nlm.nih.gov/32906212/

7. Li, Lihua, Wang, Kunpeng, Jia, Rongjun, Mo, Jinggang, Ren, Fu. 2022. Ferroportin-dependent ferroptosis induced by ellagic acid retards liver fibrosis by impairing the SNARE complexes formation. In Redox biology, 56, 102435. doi:10.1016/j.redox.2022.102435. https://pubmed.ncbi.nlm.nih.gov/36029649/