International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 111 - CHARACTERISATION OF AUDITORY AND VISUAL FUNCTION IN MOUSE MODELS OF USHER SYNDROME TYPE 1

Dr Ralph H. Holme
MRC Institute for Hearing Research
University Park
Nottingham
NG7 2RD
UK

Co-Authors: Libby RT and Steel KP
Institutions: MRC Institute for Hearing Research, University Park,

Usher syndrome type 1B and 1D, characterised by hearing loss, vestibular dysfunction and retinitis pigmentosa, are caused by mutations in myosin VIIa (MYO7A) and cadherin 23 (CDH23) respectively. Mutations in these genes also cause deafness in shaker1 and waltzer mouse mutants respectively. We have examined the sensory hair cells of the organ of Corti by scanning electron microscopy and visual function by recording electroretinograms (ERGs) in Cdh23v, Myo7a4626SB and Cdh23v/Myo7a4626SB double mutants. Outer hair cell (OHC) stereocilia of post-natal day (P) 4 +/Cdh23v and +/Myo7a4626SB controls were arranged in a precise V-shaped pattern, whereas those of Cdh23v and Myo7a4626SB homozygotes were arranged in randomly positioned clumps. Indentations in the apical surface of OHCs were apparent in Myo7a4626SB-homozygotes, but not Cdh23v-homozygotes. The a-wave component of the ERG, reflecting photoreceptor function, was reduced in amplitude by approximately 20% in both Cdh23v and Myo7a4626SB homozygotes compared to heterozygotes. No abnormalities of the retina nor cochlea were observed in double heterozygotes. Furthermore, there was no additive phenotype observed in the double homozygous mutants in either the retina or the cochlea. Finally, we found that double heterozygotes did not exhibit a significant increase in susceptibility to age-related hearing loss. Our findings show that Cdh23 and Myo7a are required for the proper organisation of the stereocilia bundle and for normal visual function. We find no evidence to suggest that mutant alleles of these genes genetically interact to affect these functions.


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