title: A Novel ENU-Induced Mutation in Myo6 Causes Vestibular Dysfunction and Deafness.
abstract: Mouse N-ethyl-N-nitrosourea (ENU) mutagenesis has generated many useful animal models for human diseases. Here we describe the identification of a novel ENU-induced mouse mutant strain Turner (Tur) that displays circling and headtossing behavior and progressive hearing loss. Tur/Tur homozygous animals lack Preyer and righting reflexes and display severe headtossing and reaching response defect. We mapped the Tur mutation to a critical region of 11 cM on chromosome 9 that includes myosin VI. Direct sequence analysis revealed a c.820A>T substitution in exon 8 of the Myo6 gene that changes amino acid Asn200 to Ile (p.N200I) in the motor domain. Analysis of inner ear hair cells by immunohistochemistry, scanning electron microscopy and histology revealed degeneration of hair cells in the inner ear and structural malformation of the stereocilia in the cochlea of Turner homozygous mutant mice. Our data indicate that this novel mouse strain provides a useful model for future studies on the function of myosin VI in mammalian auditory and non-auditory systems and in human syndromes.
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Elaine Y M
authors.initials: EY
authors.lastname: Wong
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Chelsea Y
authors.initials: CY
authors.lastname: Xu
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Manisha
authors.initials: M
authors.lastname: Brahmachary
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.|Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Pin-Xian
authors.initials: PX
authors.lastname: Xu
mesh_terms: D000818:Animals; D001309:Auditory Threshold; D001483:Base Sequence; D001522:Behavior, Animal; D033481:Chromosomes, Mammalian / Q000235:genetics; D003638:Deafness / Q000235:genetics* / Q000503:physiopathology*; D004848:Epithelium / Q000473:pathology / Q000648:ultrastructure; D005038:Ethylnitrosourea; D016057:Evoked Potentials, Auditory, Brain Stem; D005799:Genes, Dominant; D006198:Hair Cells, Auditory / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D019683:Penetrance; D014722:Vestibule, Labyrinth / Q000503:physiopathology* / Q000648:ultrastructure
chemical_list: C089785:myosin VI; D018995:Myosin Heavy Chains; D005038:Ethylnitrosourea