PT  - JOURNAL ARTICLE
AU  - Babola, Travis A.
AU  - Donovan, Naomi
AU  - Darcy, Sean S.
AU  - Spjut, Catalina D.
AU  - Kanold, Patrick O.
TI  - Limiting Hearing Loss in Transgenic Mouse Models
AID  - 10.1523/ENEURO.0465-24.2025
DP  - 2025 Feb 01
TA  - eneuro
PG  - ENEURO.0465-24.2025
VI  - 12
IP  - 2
4099  - http://www.eneuro.org/content/12/2/ENEURO.0465-24.2025.short
4100  - http://www.eneuro.org/content/12/2/ENEURO.0465-24.2025.full
SO  - eNeuro2025 Feb 01; 12
AB  - 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-Cdh23Ahl+ 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.