In this strain, the entire coding region of the endogenous BarH-like 1 (Barhl1) gene is replaced with a lacZ (β-galactosidase) reporter gene and a loxP-flanked neomycin resistance (neo) cassette, abolishing gene function. Homozygous mice are viable, fertile, and normal in size, with β-gal staining in Barhl1 expressing tissues. LacZ expression in embryos and neonates is evident in all hair cells, but is more abundantly observed in the cochlear outer hair cells. LacZ expression in adults is strong in the outer hair cells, and weak in the inner and vestibular hair cells, with persistent expression in hair cells of the organ of Corti. These mice exhibit age-related progressive degeneration of both cochlear outer and cochlear inner hair cells in the organ of Corti, resulting in hearing loss. The progression is apical-to-basal for outer hair cell and basal-to-apical for inner hair cells. Barhl1-/- mice have elevated auditory brainstem response (ABR) thresholds at all frequencies tested while some did not respond to any auditory stimuli. 2 week old Barhl1-/- mice have a reduced startle reflex and exhibit a loss of low-frequency hearing, while 3 month old mutants lose high-frequency hearing. By 6 months of age the mutants exhibit near complete loss of outer hair cells, with complete loss by 10 months, rendering the mice deaf. These Barhl1-/- mutant mice may be useful as a lacZ reporter for BARHL1 expression, and for studying age-related human deafness disorders.
