Effects of a hair cell transcription factor, Brn-3.1, gene deletion on homozygous and heterozygous mouse cochleas in adulthood and aging

The transcription factor Brn-3.1, is expressed in the inner ear hair cells throughout life and is necessary for the development of these cells. Mutant mice in which the Brn-3.1 encoding region has been deleted have no identif iable hair cells, greatly reduced numbers of spiral ganglion cells and are deaf. A mutation in the human homologue of this gene has been shown to be r elated to adult onset, sensorineural hearing loss (Vahava et al., 1998). Th e question whether haploinsufficiency in the mutant Brn-3.1 mouse with a mi xed C57BL6/129Sv genetic background could affect the adult or aged cochlear was tested, therefore, by measuring the auditory brainstem responses and e xamining the cochlea's histologically at 2, 18 and 24 months of age. The he terozygotes had a comparable hearing to the wild-type animals and similar p atterns of cochlear degeneration. Both groups showed an about 30 dB hearing loss beginning at 18 months of age, outer hair cell degeneration and loss of spiral ganglion neurons in the basal turn. There appeared to be no effec t of Brn-3.1 haploinsufficiency on the mouse cochlea, implying that one int act copy of the gene is sufficient to maintain a normal cochlea. (C) 1999 E lsevier Science B.V. All rights reserved.