Slc4a11, a member of the bicarbonate transporter family, is an electrogenic H+ transporter activated by NH3 and alkaline pH, despite not transporting bicarbonate [1]. It has been implicated in processes such as glutamine catabolism, mitochondrial superoxide regulation, and is induced by oxidative stress through NRF2 [1]. It also has potential roles in ion and water transport, and its study via genetic models like KO mouse models can offer insights into its functions.

Slc4a11 -null -mouse models recapitulate the phenotypes of congenital hereditary endothelial dystrophy (CHED), including corneal edema and hearing loss, highlighting its role in CHED pathophysiology [2]. Inducible Slc4a11 knockout in mice leads to corneal edema due to disruption of corneal endothelial pump and barrier functions, caused by mitochondrial superoxide-induced Src kinase activation [4]. These KO models show changes in oxidative damage, tight junction integrity, stromal lactate concentration, and expression of key transporters and junction proteins [5].

In conclusion, Slc4a11 plays essential roles in metabolism, oxidative stress regulation, and mitochondrial function. The Slc4a11 KO/CKO mouse models have been crucial in elucidating its role in corneal-related diseases like CHED and Fuchs endothelial corneal dystrophy, providing insights into the underlying pathophysiological mechanisms [1,2,3].

References:

1. Bonanno, Joseph A, Shyam, Raji, Choi, Moonjung, Ogando, Diego G. 2022. The H+ Transporter SLC4A11: Roles in Metabolism, Oxidative Stress and Mitochondrial Uncoupling. In Cells, 11, . doi:10.3390/cells11020197. https://pubmed.ncbi.nlm.nih.gov/35053313/

2. Patel, Sangita P, Parker, Mark D. 2015. SLC4A11 and the Pathophysiology of Congenital Hereditary Endothelial Dystrophy. In BioMed research international, 2015, 475392. doi:10.1155/2015/475392. https://pubmed.ncbi.nlm.nih.gov/26451371/

3. Tsedilina, Tatiana Romanovna, Sharova, Elena, Iakovets, Valeriia, Skorodumova, Liubov Olegovna. 2023. Systematic review of SLC4A11, ZEB1, LOXHD1, and AGBL1 variants in the development of Fuchs' endothelial corneal dystrophy. In Frontiers in medicine, 10, 1153122. doi:10.3389/fmed.2023.1153122. https://pubmed.ncbi.nlm.nih.gov/37441688/

4. Ogando, Diego G, Kim, Edward T, Li, Shimin, Bonanno, Joseph A. 2023. Corneal Edema in Inducible Slc4a11 Knockout Is Initiated by Mitochondrial Superoxide Induced Src Kinase Activation. In Cells, 12, . doi:10.3390/cells12111528. https://pubmed.ncbi.nlm.nih.gov/37296649/

5. Ogando, Diego G, Shyam, Rajalekshmy, Kim, Edward T, Liu, Chia-Yang, Bonanno, Joseph A. . Inducible Slc4a11 Knockout Triggers Corneal Edema Through Perturbation of Corneal Endothelial Pump. In Investigative ophthalmology & visual science, 62, 28. doi:10.1167/iovs.62.7.28. https://pubmed.ncbi.nlm.nih.gov/34190974/