A point mutation in a cadherin gene, Cdh23, causes deafness in a novel mutant, Waltzer Mouse Niigata

A novel mouse model for human nonsyndromic hearing loss, Waltzer niigata (v (ngt)), is found and subjected to positional cloning analysis. Genome-wide scan of 1648 backcross mice maps v(ngt) to the D10Mit258 locus near Waltzer (v). Recombination breakpoints are positioned on a physical map consisting of 13 BACs relative to the flanking markers in the vicinity of v(ngt). All elism test done in parallel shows that v(ngt) and v are allelic. Sequence a nalysis reveals one-base deletion in the cDNA encoding a cadherin-related p rotein, Cdh23, mutation of which is recently reported in v mutants. The fra me-shift change, producing a truncated protein of 51 amino acids, is ascrib ed to a base-substitution of G to A in the acceptor site of splicing juncti on which is predicted to cause one-base shift of the splicing position. (C) 2001 Academic Press.