Sequencing_of_exons_to_locate_the_mutation_in_dearisch_mice-sc-2011-06-23T09:26:46Z-674
Sequencing_of_exons_to_locate_the_mutation_in_dearisch_mice
We plan to use exome sequencing to identify the ENU-induced mutation in dearisch mutant mice We plan to use the Agilent mouse exome kit to capture the exons followed by next-generation sequencing from two mice: one from the dearisch colony that is deaf, and the other a normally-hearing mouse from the same genetic background, C3HeB/FeJ.  . This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Otitis media is the most common disease diagnosed in children and if undertreated can lead to chronic otitis media with complications such as permanent hearing loss, meningitis and even death. The World Health Organisation recognises the health burden of otitis media as being equivalent to that of polio.  It suggests that research emphasis should be placed on identifying the risk factors for otitis media.  Mouse models of otitis media, such as the ENU-induced Jeff mutant have been used to identify genes like Fbxo11 that have subsequently been shown to predispose to otitis media in humans.   The dearisch mouse mutant is also an ENU-induced mutant. It was identified as losing the Preyer reflex (ear flick in response to sound) by 5 months of age.  Auditory Brainstem Responses however, reveal that mice display hearing loss from as early as three weeks of age.  Pedigree analysis shows the threshold shift to be dominantly inherited with low penetrance. Middle ear dissections show mice with high ABR thresholds have white exudate and frequent incudomalleal fusion.  Gross inner ear anatomy, round and oval window areas and  the sensory hair cells all appear normal.   Due to the low penetrance of the phenotype normal backcross mapping of the mutation has not been possible.  Whole mouse exome sequencing is therefore being performed to identify the mutation.