LOSS OF AUDITORY FUNCTION IN TRANSGENIC MPVL7-DEFICIENT MICE

The transgenic mouse strain Mpv17 develops severe morphological degene ration of the inner ear and nephrotic syndrome at a young age (Meyer z um Gottesberge et al., 1996; Weiher et al., 1990). The audiograms (1-3 2 kHz) of Mpv17-negative mice were determined from auditory brain stem responses in young (2 months) and old (7 months) animals. Audiograms of age-matched wildtype mice with the same genetic background, but wil d-type at the Mpv17 locus, were also determined. Furthermore, young Mp v17-negative mice that carried a human Mpv17 homologue gene were studi ed. NMRI mice served as a reference for normal hearing. Mpv17-negative mice suffer from severe sensorineural hearing loss as early as 2 mont hs after birth, In the old Mpv17-negative mice no responses could be e licited at all. The 2 month old wild-type mice had normal audiograms, at 7 months only high threshold responses were seen. The poor audiogra ms of the Mpv17-negative mice are assumed to be the functional correla te of the morphological degeneration of the cochlea described earlier (Meyer zum Gottesberge et al., 1996). The finding that 2 out of 4 Mpv1 7-negative mice with the human Mpv17 gene had normal audiograms, shows that the gene inactivation can be functionally compensated by the hum an Mpv17 gene product. (C) 1997 Elsevier Science B.V.