Slc39a12, encoding the zinc transporter protein ZIP12, functions to transport zinc across cellular membranes, including influx across the plasma membrane. Zinc is essential for numerous biological processes, and thus, Slc39a12 is of great biological importance, especially in the vertebrate nervous system where it is highly abundant [1,3,4].

In Xenopus tropicalis, ZIP12 depletion by antisense morpholinos leads to anterior neural tube defects and embryonic lethality, indicating its crucial role in neural tube closure and embryonic development [1,3]. In mouse neural cells, ZIP12 knockdown impairs neurite outgrowth and mitochondrial function, and also reduces cAMP response element-binding protein activation and tubulin polymerization [1,3]. In rats, loss of Slc39a12 in hippocampal neurons due to temporomandibular joint osteoarthritis (TMJ-OA) results in cellular oxidative stress, neuronal damage, and anxiety-like behavior [2].

In conclusion, Slc39a12 is essential for nervous system development and function, as demonstrated by animal models. Its role in processes like neural tube closure, neurite outgrowth, and mitochondrial function in neurons is significant. Moreover, its dysregulation in hippocampal neurons is associated with anxiety-like behavior in rats with TMJ-OA, highlighting its potential link to neurological and psychiatric diseases [1,2,3].

References:

1. Davis, Danielle N, Strong, Morgan D, Chambers, Emily, Lin, Dingbo, Chowanadisai, Winyoo. 2021. A role for zinc transporter gene SLC39A12 in the nervous system and beyond. In Gene, 799, 145824. doi:10.1016/j.gene.2021.145824. https://pubmed.ncbi.nlm.nih.gov/34252531/

2. Shen, Zhenguo, Fan, Chenyu, Ding, Chunmeng, Wang, Yuanyin, Xing, Tian. 2024. Loss of Slc39a12 in hippocampal neurons is responsible for anxiety-like behavior caused by temporomandibular joint osteoarthritis. In Heliyon, 10, e26271. doi:10.1016/j.heliyon.2024.e26271. https://pubmed.ncbi.nlm.nih.gov/38375280/

3. Chowanadisai, Winyoo, Graham, David M, Keen, Carl L, Rucker, Robert B, Messerli, Mark A. 2013. Neurulation and neurite extension require the zinc transporter ZIP12 (slc39a12). In Proceedings of the National Academy of Sciences of the United States of America, 110, 9903-8. doi:10.1073/pnas.1222142110. https://pubmed.ncbi.nlm.nih.gov/23716681/

4. Chowanadisai, Winyoo. 2014. Comparative genomic analysis of slc39a12/ZIP12: insight into a zinc transporter required for vertebrate nervous system development. In PloS one, 9, e111535. doi:10.1371/journal.pone.0111535. https://pubmed.ncbi.nlm.nih.gov/25375179/