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© Research
Publication : Mammalian genome : official journal of the International Mammalian Genome Society

Twister mutant mice are defective for otogelin, a component specific to inner ear acellular membranes

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Mammalian genome : official journal of the International Mammalian Genome Society - 01 Nov 2000

Simmler MC, Zwaenepoel , Verpy E, Guillaud L, Elbaz C, Petit C, Panthier JJ

Link to Pubmed [PMID] – 11178734

Mamm. Genome 2000 Nov;11(11):961-966

Deafness is a common sensory defect in human. Our understanding of the molecular bases of this pathology comes from the study of a few genes that have been identified in human and/or in mice. Indeed, deaf mouse mutants are good models for studying and identifying genes involved in human hereditary hearing loss. Among these mouse mutants, twister was initially reported to have abnormal behavior and thereafter to be deaf. The recessive twister (twt) mutation has been mapped on mouse Chromosome (Chr) 7, homologous to the long arm of human Chr 15 (15q11). Otog, the gene encoding otogelin, a glycoprotein specific to all the acellular membranes of the inner ear, is also localized to mouse Chr 7, but in a region more proximal to the twister mutation, homologous to the short arm of human Chr 11 (11p15) carrying the two deafness loci, DFNB18 and USH1C. Mutant mice resulting from the knock-out of Otog, the Otog(tm1Prs) mice, present deafness and severe imbalance. Although twt had been mapped distally to Otog, these data prompted us to test whether twt could be due to a mutation in the Otog locus. Here, we demonstrate by genetic analysis that twt is actually allelic to Otog(tm1Prs). We further extend the phenotypical analysis of twister mice, documenting the association of a severe vestibular phenotype and moderate to severe form of deafness. Molecular analysis of the Otog gene revealed the absence of detectable expression of Otog in the twister mutant. The molecular and phenotypical description of the twt mouse mutation, Otog(twt), reported herein, highlights the importance of the acellular membranes in the inner ear mechanotransduction process. </hea

http://www.ncbi.nlm.nih.gov/pubmed/11178734