Tmem63b-flox Mouse

Tmem63b encodes a highly conserved stretch-activated ion channel. It functions as an osmosensor and mechanosensor, converting physical forces into electrical signals or triggering intracellular cascades. This is crucial for cells to respond to osmotic and mechanical stress, participating in various biological processes such as maintaining body fluid homeostasis, facilitating surfactant secretion, and regulating cell volume [1-4, 7-9].

In gene-knockout (KO) mouse models, deletion of Tmem63b in subfornical organ (SFO) neurons impaired hyperosmolarity-induced drinking behavior, indicating its role in thirst drive [2,6]. In inner ear sensory hair cells, genetic deletion led to necroptosis of outer hair cells and progressive hearing loss, suggesting its importance in hearing [4]. In intestinal stem cells, its deletion decelerated intestinal motility, impaired digestion, and attenuated cell proliferation [5]. In alveolar type 2 epithelial cells, loss of Tmem63b (along with Tmem63a) resulted in atelectasis and respiratory failure due to surfactant secretion deficit [3]. In humans, heterozygous variants of Tmem63b were found in individuals with severe early-onset developmental and epileptic encephalopathy, intellectual disability, and hematological abnormalities [1].

In conclusion, Tmem63b is essential for multiple biological functions including osmoregulation, hearing, intestinal function, and surfactant secretion. Studies using KO mouse models have revealed its role in these processes and in related disease conditions such as encephalopathies. Understanding Tmem63b provides insights into the underlying mechanisms of these biological functions and diseases.