Slc9a1-flox Mouse

Slc9a1, encoding the sodium/hydrogen exchanger isoform one (NHE1), is crucial for maintaining intracellular pH homeostasis by exchanging one intracellular proton for one extracellular sodium ion [3,4]. This process is involved in multiple biological pathways and is of great biological importance. Genetic models, such as knockout mouse models, have been valuable in studying its functions.

In conditional Slc9a1 knockout (cKO) mouse models, deletion of Slc9a1 in Cx3cr1+ cells led to expansion of a microglial subgroup with elevated transcription of white matter myelination genes. This subgroup also showed more acidic pHi and upregulated CREB signaling. Moreover, there was an enrichment of a corresponding oligodendrocyte subgroup in the white matter tissues, indicating stimulation of microglia-oligodendrocyte crosstalk for remyelination [1].

In mice, the Slc9a1 inhibitor decreased the transport efficiency of chitosan oligosaccharide (COS) both in vitro and in vivo, and overexpression of Slc9a1 in MODE-K cells increased COS transport, suggesting its role in COS transport across the intestinal mucosa [2].

Mice with a homozygous null mutation in Slc9a1 exhibited ataxia, recurrent seizures, and selective neuronal cell death, and in humans, mutations in SLC9A1 are associated with cerebellar ataxia, sensorineural hearing loss, and neuromuscular disorders [3,4].

In gliomas, higher SLC9A1 mRNA levels in higher-grade gliomas were correlated with worsened survival probabilities, and inhibition of NHE1 protein reduced glioma volume and invasion in mouse models [5]. Adipose mesenchymal stem cell-derived exosomal microRNA-1236 reduced breast cancer cells' resistance to cisplatin by suppressing SLC9A1 [6].

In conclusion, Slc9a1 plays essential roles in maintaining intracellular pH, microglia-oligodendrocyte crosstalk, intestinal transport, and is associated with various diseases including neurological disorders and cancers. The Slc9a1 KO/CKO mouse models have significantly contributed to understanding its functions in these disease-related biological processes.