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Publication : Limiting Hearing Loss in Transgenic Mouse Models.

First Author  Babola TA Year  2025
Journal  eNeuro Volume  12
Issue  2 PubMed ID  39900508
Mgi Jnum  J:371563 Mgi Id  MGI:7869132
Doi  10.1523/ENEURO.0465-24.2025 Citation  Babola TA, et al. (2025) Limiting Hearing Loss in Transgenic Mouse Models. eNeuro 12(2):ENEURO.0465-24.2025
abstractText  Transgenic mice provide unprecedented access to manipulate and visualize neural circuits; however, those on a C57BL/6 background develop progressive hearing loss, significantly confounding systems-level and behavioral analysis. While outbreeding can limit hearing loss, it introduces strain variability and complicates the generation of complex genotypes. Here, we propose an approach to preserve hearing by crossing transgenic mice with congenic B6.CAST-Cdh23(Ahl) (+) mice, which maintain low-threshold hearing into adulthood. Widefield and two-photon imaging of the auditory cortex revealed that 2.5-month-old C57BL/6 mice exhibit elevated thresholds to high-frequency tones and widespread cortical reorganization, with most neurons responding best to lower frequencies. In contrast, Ahl+ C57BL/6 mice exhibited robust neural responses across tested frequencies and sound levels (4-64 kHz, 30-90 dB SPL) and retained low thresholds into adulthood. Our approach offers a cost-effective solution for generating complex genotypes and facilitates more interpretable systems neuroscience research by eliminating confounding effects from hearing loss.
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