Cabp2-flox Mouse

Cabp2, also known as calcium-binding protein 2, is a potent modulator of inner hair cell (IHC) voltage-gated calcium channels CaV1.3 [1]. It belongs to the Ca2+ binding protein family related to calmodulin and is highly expressed in the cochlea. By inhibiting the inactivation of CaV1.3 channels, it sustains the availability of these channels for synaptic sound encoding [3].

In Cabp2 -knockout (Cabp2 KO) mice, there are significant auditory brainstem response (ABR) threshold elevations at 4 weeks of age, which become more severe in the mid-frequency range by 9 weeks. Distortion product otoacoustic emissions (DPOAEs), normal at 4 weeks, are significantly reduced in the mid-frequency range by 9 weeks. Recordings from single spiral ganglion neurons (SGNs) show reduced spontaneous and sound-evoked firing rates [2,3]. Gene therapy using AAV2/1 and AAV-PHP.eB viral vectors to deliver the Cabp2 coding sequence into IHCs of early postnatal Cabp2 -/- mice can restore IHC CaV1.3 function and improve hearing, proving the feasibility of DFNB93 gene therapy [1].

In conclusion, Cabp2 is crucial for normal auditory function, especially in maintaining the proper function of IHC voltage-gated calcium channels. Studies on Cabp2 KO mouse models have revealed its role in auditory synaptopathies like DFNB93, providing a basis for potential gene-therapy-based treatments for related hearing impairments [1,2,3].