Slc4a10-flox Mouse

Slc4a10, also known as NBCn2 or NCBE, is a plasma-membrane bound transporter. It utilizes the Na+ gradient to drive cellular HCO3-uptake, mediating acid extrusion. It is involved in cation-coupled bicarbonate transport pathways, which are crucial for intracellular pH control, transcellular movement of acid-base equivalents, and are essential for diverse tissue functions including neuronal discharge and sensory neuron development [4]. Mouse models have been valuable for studying its function.

Slc4a10 knockout (KO) mice display multiple phenotypes. They have collapsed brain ventricles, suggesting its importance in cerebrospinal fluid (CSF) production [1,2,6]. These mice also show mild behavioral abnormalities, delayed habituation, and alterations in the two-object novel object recognition task [1]. Functionally, the release of the inhibitory neurotransmitter GABA is compromised in Slc4a10-/-mice, while glutamate release is preserved, indicating its role in inhibitory synaptic transmission [1]. Additionally, Slc4a10 KO mice have early-onset progressive hearing loss, reduced endocochlear potential, and outer hair cell degeneration, highlighting its role in inner ear homeostasis [3]. In terms of neuronal excitability, disruption of Slc4a10 augments neuronal excitability and modulates synaptic short-term plasticity in the hippocampus and neocortex [5].

In conclusion, Slc4a10 is essential for multiple biological processes. Through KO mouse models, its role in CSF production, neuronal function including synaptic transmission and excitability, and inner ear homeostasis has been revealed. These findings are relevant to understanding neurodevelopmental disorders, as biallelic loss-of-function variants in SLC4A10 in humans cause a neurodevelopmental disorder with features like hypotonia, delayed psychomotor development, and intellectual impairment [1,2].