The original shaker-with-syndactylism mutation (sy) is a contiguous gene deletion syndrome

摘要

Tests for allelism among mice with four different mutant alleles at the shaker-with-syndactylism locus on mouse Chromosome (Chr) 18 provide evidence that the original radiation-induced mutation, sy, is a deletion including at least two genes associated with distinct phenotypes. Mice homozygous for sy have syndactylous feet and other skeletal malformations, are deaf, and exhibit abnormal behavior characteristic of vestibular dysfunction. Two less severe spontaneous mutations, shown to be allelic with sy, cause syndactylism when homozygous (hence named fused phalanges, sy ^fp and sy ^fp-2J), but do not affect hearing and behavior. Here we describe a third spontaneous mutation allelic with sy that does not affect foot morphology (hence named no syndactylism, sy^ns), but that does cause deafness and balance defects when homozygous. Complementation test results indicate that sy ^fp and sy ^fp-2J are alleles of the same gene, but that sy^ns is an allele of a different gene. The original sy mutation, therefore, includes both of the genes defined by these three spontaneous mutations. Typing of DNA markers in sy/sy mice revealed a deletion of approximately 1 cM in the sy region of Chr 18, including D18Mit52, D18Mit124, D18Mit181, and D18Mit205. The genetic relationships described here will aid in positional cloning efforts to identify the genes responsible for the disparate phenotypes associated with the sy locus.