International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 175 - TWO QUANTITATIVE TRAIT LOCI AFFECTING PROGRESSIVE HEARING LOSS IN 101/H MICE

Mashimo T
Kyoto University

Co-Authors: 3) Erven A, 3) Steel KP, 2) Guénet J L
Institutions: 2) Institut Pasteur, 3) MRC

Although recent progress in identifying genes involved in deafness has been remarkable, the genetic basis of progressive hearing loss (or age-related hearing loss) is poorly understood because of the extreme difficulty in studying such a late-onset, complex disease in human populations. Mice offer a promising approach for the genetic study of these human diseases because of their short life span, ease of experimental manipulation, and limited genetic heterogeneity.

Several inbred strains of mice, such as 129P1/ReJ, C57BL/6J, DBA/2J, BALB/cByJ, have been so far reported to exhibit age-related hearing loss (AHL) and provide valuable models for human non-syndromic deafness. Here we show that 101/H mice also exhibit severe deafness with early onset. MAI/Pas and MBT/Pas mice derived from recently trapped wild mice exhibited normal auditory behaviour.

Linkage analysis of F2 populations derived from crosses between the 101/H and the wild mice suggested at least two major QTLs that influence progressive hearing loss. A first QTL, designated Phl1, was mapped with a highest Lod score of 6.0 at a telomeric region of chromosome 17, where no deafness-related QTL has been mapped so far. A second QTL, designated Phl2, mapped on chromosome 10 exhibited a highest Lod score of 6.1. The map position of Phl2 near the well-known QTL of age-related hearing loss (Ahl) suggested the possibility of allelism. Finally, we found some evidence of epistatic interaction between Phl1 and Phl2.


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