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Loss of auditory function in transgenic Mpv17-deficient mice
M Müller1, J W Smolders, A M Meyer zum Gottesberge
1Klinikum der J.W. Goethe-Universität, Physiologisches Institut III, Frankfurt am Main, Germany. m.mueller@em.uni-frankfurt.de
Abstract:
The transgenic mouse strain Mpv17 develops severe morphological degeneration of the inner ear and nephrotic syndrome at a young age (Meyer zum Gottesberge et al., 1996; Weiher et al., 1990). The audiograms (1-32 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 wild-type mice with the same genetic background, but wild-type at the Mpv17 locus, were also determined. Furthermore, young Mpv17-negative mice that carried a human Mpv17 homologue gene were studied. NMRI mice served as a reference for normal hearing. Mpv17-negative mice suffer from severe sensorineural hearing loss as early as 2 months after birth. In the old Mpv17-negative mice no responses could be elicited at all. The 2 month old wild-type mice had normal audiograms, at 7 months only high threshold responses were seen. The poor audiograms of the Mpv17-negative mice are assumed to be the functional correlate of the morphological degeneration of the cochlea described earlier (Meyer zum Gottesberge et al., 1996). The finding that 2 out of 4 Mpv17-negative mice with the human Mpv17 gene had normal audiograms, shows that the gene inactivation can be functionally compensated by the human Mpv17 gene product.
Insights
Mpv17-negative mice exhibit severe hearing loss due to inner ear degeneration. The human Mpv17 gene can functionally compensate for this gene inactivation, restoring normal hearing in affected mice.
Area of Science:
- Genetics
- Neuroscience
- Otolaryngology
Background:
- The Mpv17 mouse strain exhibits inner ear degeneration and nephrotic syndrome.
- Mpv17 gene inactivation leads to progressive sensorineural hearing loss.
Purpose of the Study:
- To assess hearing function in Mpv17-negative mice.
- To investigate the effect of the human Mpv17 homologue gene on hearing.
- To correlate auditory brain stem responses with inner ear morphology.
Main Methods:
- Auditory brain stem responses (ABRs) were used to determine audiograms in Mpv17-negative and wild-type mice.
- Hearing was assessed in young (2 months) and old (7 months) animals.
- Mpv17-negative mice carrying a human Mpv17 homologue gene were also studied.
Main Results:
- Mpv17-negative mice showed severe sensorineural hearing loss by 2 months of age, with no response in older animals.
- Wild-type mice had normal hearing at 2 months, with high-threshold responses at 7 months.
- Two of four Mpv17-negative mice with the human Mpv17 gene displayed normal audiograms.
Conclusions:
- Mpv17 gene inactivation causes significant hearing impairment, correlating with cochlear degeneration.
- The human Mpv17 gene product can functionally compensate for the loss of the mouse Mpv17 gene.
- This suggests a conserved function of the Mpv17 gene in hearing.