High-resolution mapping of tlt, a mouse mutant lacking otoconia

The ability to sense gravity is enhanced by an extracellular structure that overlies the macular sensory epithelium. This complex consists of high den sity particles, otoconia, embedded within a gelatinous membrane. The tilted mouse specifically lacks otoconia, yet has no other detectable anatomic le sions. Furthermore, the penetrance of the tilted phenotype is nearly 100%. This mouse provides a model to identify genes that are involved in the deve lopment and function of vestibular otoconia. Using SSLP markers, we have ma pped the tilted (tlt) gene on mouse Chromosome (Chr) 5 between D5Mit421 and D5Mit353/D5Mit128/ D5Mit266/D5Mit267 by analysis of the progeny of an inte rsub-specific F-2 intercross. We also mapped the fibroblast growth factor r eceptor 3 (Fgfr3) gene, a potential candidate for tlt, and the Huntington's disease homolog (Hdh) gene to D5Mit268, approximately 4.3 centiMorgans (cM ) from the tilted locus. This study excludes both Fgfr3 and Hdh as candidat e genes for tlt and identifies closely linked microsatellite markers that w ill be useful for the positional cloning of tlt.