International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 181 - A POINT MUTATION IN A NOVEL TYPE OF CADHERIN, CDH23 CAUSES DEAFNESS IN WALTZER MOUSE NIIGATA

Dr. Yuichi Wakabayashi
Niigata University Graduate School of Medical and Dental sciences
1-757 Asahimachi
Niigata
951-8122
Japan

Co- Authors: Wada T, Yagi M, Kominami R
Institutions: Niigata University Graduate School of Medical & Dental Sciences, Div. of Molecular Biology

“A point mutation in a novel type of cadherin, Cdh23 causes deafness in Waltzer mouse Niigata”  Waltzer mouse Niigata(vngt) is a novel deaf mutation which arose spontaneously in ICR background. Homozygotes exhibit profound hearing loss examined by ABR(auditory brain stem response)as well as hyperactivity, head tossing and circling behavior. Linkage analysis using 1600 backcross mice showed that vngt was mapped in the vicinity of D10Mit258, which was closely linked to Waltzer(v). A physical map with 13 BACs containing this region was constructed, and further linkage analysis using STS markers of the BACs revealed that the critical region was within a two-BAC region. Sequencing of the BACs proveded five ESTs, one of which was a part of Cdh23 encoding a novel type of cadherin. Early in this year mutations in Cdh23 were reported in v mutants (Palma D et al 2001 Nat.Genet.) and allelism test showed that vngt and v are allelic. Mutation analysis of Cdh23 cDNA revealed one base deletion that led to a frame-shift mutation, which was predicted to produce a truncated protein of 51 amino acids. This change at the cDNA lebel was due to a base substitution of G to A in the acceptor site of the splicing junction at the genomic level, which resulted in one base shift of the splicing position (Wada T et al 2001 BBRC). Interestingly, age related hearling loss(AHL) was reported to be closely linked to v locus (Johnson K.R.et al 2000 Genomics ). Although all mutations detected in v mutants are  null, other less severe allelic forms of Cdh23 might cause AHL. The relationship between Cdh23 and AHL is now under investigation.


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