BCH3031 Lecture Notes - Lecture 19: Vestibular System, Semicircular Canals, Taxis
25 May 2018
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Lecture 19 – Hearing and Deafness (Forward genetics screening)
• 250 million people worldwide have congenitcal hearing impairment
• 50% of these have genetic basis
• 70% of cases are non-syndromic (not associated with any other pathology)
• 60% of adults older than 70 have significant hearing los
• Deafness is also associated with vestibular (balance defects) because ear also
affects spatial perception
Why use Mice to Study Hearing?
• Tractability
o Gene identity
o Anatomy/physiology – ears very similar to human ears
o Utility – easy to tell if a mouse is deaf
o Genomics – mapping and identifying mutations in mouse using inbred
mouse stains
• Major motivations for undertaking Screen in Mice
o Model disease and to understand human hearing
▪ Relate genetic variation with structural changes
o Mice can help find genes which cause deafness
How does the Ear Work?
• Sound waves distort tympanic membrane
• Cochlea in inner ear
o Semicircular canals important for
telling which waves go up or down
o Changes in pressure
o Comprised of scala vestibule, scala
tympani
• Organ of corti
o Stereocilia is displaced – depolarize →
interact with neurons → direct to brain
E.g. Harwell Screening (dominant screening)
• Chemical ENU – induced mutations in germline of testes → goes into blood
stream and testes → transfer gametes when bred with other mice → form G1
mice which is screened
Screening for Deafness and Vestibular Defect in Mice
1. Clickbox test
o Emits high frequency sound → causes them to flick their ears back
2. Negative geotaxis test
o Test vestibular function
o Vestibular defect – doesn’t know which way is up or down
3. Righting test
o Testing vestibular function
How do you Identify the Causative Mutation?
• In bred mice – genetically identical
• 3 will inherit part of chromosome that carries mutation – dominant mutation
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