Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss.
Age-related hearing loss (AHL) in common inbred mouse strains is a genetically complex quantitative trait. We found a synonymous single-nucleotide polymorphism in exon 7 of Cdh23 that shows significant association with AHL and the deafness modifier mdfw (modifer of deafwaddler). The hypomorphic Cdh23(753A) allele causes in-frame skipping of exon 7. Altered adhesion or reduced stability of CDH23 may confer susceptibility to AHL. Homozygosity at Cdh23(753A) or in combination with heterogeneous secondary factors is a primary determinant of AHL in mice.
Noben-Trauth
Konrad
K
Section on Neurogenetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, Maryland 20850, USA. nobentk@nidcd.nih.gov
Zheng
Qing Yin
QY
Johnson
Kenneth R
KR
D000375:Aging; D000483:Alleles; D000818:Animals; D015820:Cadherins / Q000235:genetics* / Q000502:physiology; D019976:Cloning, Organism; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D040582:Inheritance Patterns; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D020641:Polymorphism, Single Nucleotide
D015820:Cadherins; C499091:Cdh23 protein, mouse