Tmem163-KO Mouse

TMEM163, also potentially known as ZNT11, is a zinc efflux transporter. It belongs to the mammalian solute carrier 30 (SLC30) family of the cation diffusion facilitator (CDF) protein superfamily. Zinc and its transporters play vital roles in human health, and TMEM163 is involved in maintaining zinc homeostasis in cells. It may also interact with other SLC30 zinc efflux transporters, increasing the functional diversity of zinc effluxers in specific tissues or cell types [1,2,5].

Functional zinc flux assays in HeLa cells expressing TMEM163 protein variants (L76R and L76P) showed distinct attenuation or enhancement of zinc efflux respectively. Zebrafish models with knockdown of tmem163a and tmem163b (morphants) demonstrated that loss of tmem163 causes dysplasia of the larvae, locomotor disability, myelin deficit, poor oligodendrocyte proliferation, elevated apoptosis, and reduced oligodendrocytes and neurons. Expression of human wild-type TMEM163 mRNAs in morphants rescued the phenotype, while the TMEM163 L76P and L76R mutants aggravated the condition [3].

In conclusion, TMEM163 is crucial for zinc efflux and maintaining zinc homeostasis. Through functional studies in zebrafish models, it has been shown to play a role in myelin development. Mutations in TMEM163 can lead to hypomyelinating leukodystrophy, highlighting its importance in oligodendrocyte development and myelin formation [3,4].

References:

1. Styrpejko, Daniel J, Cuajungco, Math P. 2021. Transmembrane 163 (TMEM163) Protein: A New Member of the Zinc Efflux Transporter Family. In Biomedicines, 9, . doi:10.3390/biomedicines9020220. https://pubmed.ncbi.nlm.nih.gov/33670071/

2. Sanchez, Vanessa B, Ali, Saima, Escobar, Adrian, Cuajungco, Math P. 2019. Transmembrane 163 (TMEM163) protein effluxes zinc. In Archives of biochemistry and biophysics, 677, 108166. doi:10.1016/j.abb.2019.108166. https://pubmed.ncbi.nlm.nih.gov/31697912/

3. Yan, Huifang, Yang, Shuyan, Hou, Yiming, Cuajungco, Math P, Wang, Jingmin. 2022. Functional Study of TMEM163 Gene Variants Associated with Hypomyelination Leukodystrophy. In Cells, 11, . doi:10.3390/cells11081285. https://pubmed.ncbi.nlm.nih.gov/35455965/

4. do Rosario, Michelle C, Bey, Guillermo Rodriguez, Nmezi, Bruce, Padiath, Quasar Saleem, Shukla, Anju. . Variants in the zinc transporter TMEM163 cause a hypomyelinating leukodystrophy. In Brain : a journal of neurology, 145, 4202-4209. doi:10.1093/brain/awac295. https://pubmed.ncbi.nlm.nih.gov/35953447/

5. Escobar, Adrian, Styrpejko, Daniel J, Ali, Saima, Cuajungco, Math P. 2022. Transmembrane 163 (TMEM163) protein interacts with specific mammalian SLC30 zinc efflux transporter family members. In Biochemistry and biophysics reports, 32, 101362. doi:10.1016/j.bbrep.2022.101362. https://pubmed.ncbi.nlm.nih.gov/36204728/