title: High-resolution mapping of tlt, a mouse mutant lacking otoconia.
abstract: The ability to sense gravity is enhanced by an extracellular structure that overlies the macular sensory epithelium. This complex consists of high density particles, otoconia, embedded within a gelatinous membrane. The tilted mouse specifically lacks otoconia, yet has no other detectable anatomic lesions. Furthermore, the penetrance of the tilted phenotype is nearly 100%. This mouse provides a model to identify genes that are involved in the development and function of vestibular otoconia. Using SSLP markers, we have mapped the tilted (tlt) gene on mouse Chromosome (Chr) 5 between D5Mit421 and D5Mit353/D5Mit128/D5Mit266/D5Mit267 by analysis of the progeny of an intersubspecific F2 intercross. We also mapped the fibroblast growth factor receptor 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 candidate genes for tlt and identifies closely linked microsatellite markers that will be useful for the positional cloning of tlt.
authors.affiliation: Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: H C
authors.initials: HC
authors.lastname: Ying
authors.forename: B
authors.initials: B
authors.lastname: Hurlé
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: B A
authors.initials: BA
authors.lastname: Bohne
authors.forename: M K
authors.initials: MK
authors.lastname: Wuerffel
authors.forename: D M
authors.initials: DM
authors.lastname: Ornitz
mesh_terms: D000818:Animals; D002503:Centromere; D003433:Crosses, Genetic; D005819:Genetic Markers; D000071058:Huntingtin Protein; D008540:Meiosis; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010037:Otolithic Membrane / Q000002:abnormalities*; D020161:Physical Chromosome Mapping / Q000379:methods*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D013550:Swimming / Q000502:physiology
chemical_list: D005819:Genetic Markers; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D017468:Receptors, Fibroblast Growth Factor; C496366:Fgfr3 protein, mouse; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3