Non-syndromic vestibular disorder with otoconial agenesis in tilted/mergulhador mice caused by mutations in otopetrin 1

Belen Hurle, Elena Ignatova, Silvia M. Massironi, Tomoji Mashimo, Xavier Rios, Isolde Thalmann, Ruediger Thalmann, David M. Ornitz

Research output: Contribution to journalReview articlepeer-review

79 Scopus citations

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, Ala151→Glu in TM3; mlh, Leu408→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.

Original languageEnglish
Pages (from-to)777-789
Number of pages13
JournalHuman molecular genetics
Volume12
Issue number7
DOIs
StatePublished - Apr 1 2003

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