Atp13a5 is a member of the P5-ATPase group of genes in mammals. It belongs to a family of poorly characterized cation-transporting ATPases with unknown substrate specificity [2,4,5]. It is expressed most highly in the adult mouse brain, with fairly constant levels between different brain regions such as the cerebral cortex, hippocampus, brainstem, and cerebellum [2]. It may also play a role in certain disease-related processes, as it has been identified as a candidate gene for allergic dermatitis [3], and SNPs in the gene were detected in a family with atypical Hailey-Hailey disease [7]. Its expression has also been associated with salivary metabolite levels, specifically creatinine [6].

A knock-in mouse model with both tdTomato reporter and Cre recombinase for Atp13a5 has been generated. This model has revealed that Atp13a5 is a specific marker of the central nervous system (CNS) pericyte lineage. Atp13a5-positive pericytes start to appear around murine embryonic day 15 (E15) and expand along the cerebrovasculature. The tdTomato reporter reliably labels CNS pericytes in the spinal cord and retina but not in peripheral organs, suggesting that brain pericytes may be shaped by the developing neural environment [1].

In conclusion, Atp13a5 is significant in identifying CNS pericyte lineage. The Atp13a5-based mouse model provides a reliable tool to explore pericyte heterogeneity and blood-brain barrier (BBB) functions in health and diseases. Its potential role in allergic dermatitis and its association with salivary metabolites and a skin disease (Hailey-Hailey disease) also highlight its importance in understanding disease mechanisms [1,3,6,7].

References:

1. Guo, Xinying, Xia, Shangzhou, Ge, Tenghuan, Ma, Qingyi, Zhao, Zhen. 2024. Atp13a5 Marker Reveals Pericyte Specification in the Mouse Central Nervous System. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 44, . doi:10.1523/JNEUROSCI.0727-24.2024. https://pubmed.ncbi.nlm.nih.gov/39261008/

2. Weingarten, Lisa S, Dave, Hardi, Li, Hongyan, Crawford, Dorota A. 2011. Developmental expression of P5 ATPase mRNA in the mouse. In Cellular & molecular biology letters, 17, 153-70. doi:10.2478/s11658-011-0039-3. https://pubmed.ncbi.nlm.nih.gov/22207337/

3. Jin, Lei, Deng, Lin, Wang, Wanchun. 2022. Candidate Genes of Allergic Dermatitis Are Associated with Immune Response. In Journal of healthcare engineering, 2022, 8745722. doi:10.1155/2022/8745722. https://pubmed.ncbi.nlm.nih.gov/35028126/

4. Schultheis, Patrick J, Hagen, Tamara T, O'Toole, Kate K, Okunade, Gbolahan W, Shull, Gary E. . Characterization of the P5 subfamily of P-type transport ATPases in mice. In Biochemical and biophysical research communications, 323, 731-8. doi:. https://pubmed.ncbi.nlm.nih.gov/15381061/

5. Sørensen, Danny Mollerup, Holemans, Tine, van Veen, Sarah, Palmgren, Michael, Vangheluwe, Peter. 2018. Parkinson disease related ATP13A2 evolved early in animal evolution. In PloS one, 13, e0193228. doi:10.1371/journal.pone.0193228. https://pubmed.ncbi.nlm.nih.gov/29505581/

6. Nag, Abhishek, Kurushima, Yuko, Bowyer, Ruth C E, Menni, Cristina, Steves, Claire J. . Genome-wide scan identifies novel genetic loci regulating salivary metabolite levels. In Human molecular genetics, 29, 864-875. doi:10.1093/hmg/ddz308. https://pubmed.ncbi.nlm.nih.gov/31960908/

7. van Beek, Nina, Patsatsi, Aikaterini, Gupta, Yask, Schmidt, Enno, Ibrahim, Saleh. 2015. A family with atypical Hailey Hailey disease--is there more to the underlying genetics than ATP2C1? In PloS one, 10, e0121253. doi:10.1371/journal.pone.0121253. https://pubmed.ncbi.nlm.nih.gov/25837627/