International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


Minowa O, Inoue M, Sakuraba Y, Motegi H,  Toki H, Tada M, Kaneda H, Ishijima J, Masuya H, Kobayashi K, Suzuki T, Wakana S, Gondo Y, Shiroishi T, Noda T

RIKEN-GSC, Yokohama, Japan

  Development of syndromic and nonsyndromic deafness mouse models would greatly facilitate understanding the mechanisms of hearing impairment; the models would be useful tools to advance current methods of diagnosis and treatment of hearing impairment. In order to develop a novel human hereditary deafness mouse model, we used a ENU-mutagenesis screening platform established to identify various kinds of mouse models for human diseases. We extensively evaluated various visible, clinical, biochemical, hematological, and cardiovascular phenotypes as well as behavioral anomalies and tumorigenesis.

  Specifically, we performed primary screening for hearing impairment by observing the startle responses evoked by click box stimulation during the modified-SHIRPA procedure. Of the 5,000 G1 mice screened, 14 G1 mutant candidates were subjected to the auditory brainstem response (ABR) measurements to analyze the early phases of auditory function impairment. Of these 14 mutant candidates, 11 G1 mice showed ABR abnormalities and they had been clearly inherited by G2 generations. The heritable hearing phenotype had not been accompanied by any behavioral or other traits, which is compatible with human diagnostic-type nonsyndromic deafness. The threshold ABR values in these G1 founders varied in mice with slight hearing impairment to those with complete hearing loss, suggesting that multiple causative genes and/or a variety of alleles of certain genes exist among the mutants.

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