PUBLICATION
Non-syndromic vestibular disorder with otoconial agenesis in tilted/mergulhador mice caused by mutations in otopetrin 1
- Authors
- Hurle, B., Ignatova, E., Massironi, S.M., Mashimo, T., Rios, X., Thalmann, I., Thalmann, R., and Ornitz, D.M.
- ID
- ZDB-PUB-031020-1
- Date
- 2003
- Source
- Human molecular genetics 12(7): 777-789 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Immunohistochemistry
- Drosophila melanogaster
- Humans
- Mice, Inbred C57BL
- DNA Primers/chemistry
- Sequence Homology, Amino Acid
- Mice, Inbred BALB C
- Genes, Recessive
- DNA, Complementary/metabolism
- Vestibular Diseases/genetics*
- Vestibular Diseases/pathology*
- Ear, Inner/embryology*
- Ear, Inner/metabolism*
- Alleles
- Amino Acid Sequence
- In Situ Hybridization
- Physical Chromosome Mapping
- Transcription, Genetic
- Mice
- Cell Membrane/metabolism
- Mutation*
- Multigene Family
- Protein Structure, Tertiary
- RNA, Messenger/metabolism
- Haplotypes
- Caenorhabditis elegans
- Models, Genetic
- Protein Structure, Secondary
- Molecular Sequence Data
- Membrane Proteins/genetics
- Membrane Proteins/physiology*
- Point Mutation
- Animals
- PubMed
- 12651873 Full text @ Hum. Mol. Genet.
Citation
Hurle, B., Ignatova, E., Massironi, S.M., Mashimo, T., Rios, X., Thalmann, I., Thalmann, R., and Ornitz, D.M. (2003) Non-syndromic vestibular disorder with otoconial agenesis in tilted/mergulhador mice caused by mutations in otopetrin 1. Human molecular genetics. 12(7):777-789.
Abstract
Otoconia are biominerals within the utricle and saccule of the inner ear that are critical for the perception of gravity and linear acceleration. The classical mouse mutant tilted (tlt) and a new allele, mergulhador (mlh), are recessive mutations that affect balance by impairing otoconial morphogenesis without causing collateral deafness. The mechanisms governing otoconial biosynthesis are not known. Here we show that tlt and mlh are mutant alleles of a novel gene (Otopetrin 1, Otop1), encoding a multi-transmembrane domain protein that is expressed in the macula of the developing otocyst. Both mutants carry single point mutations leading to non-conservative amino acid substitutions that affect two putative transmembrane (TM) domains (tlt, Ala(151)-->Glu in TM3; mlh, Leu(408)-->Gln in TM8). Otop1 and Otop1-like paralogues, Otop2 and Otop3, define a new gene family with homology to the C. elegans and D. melanoganster DUF270 genes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping