title: Characterization of the human and mouse unconventional myosin XV genes responsible for hereditary deafness DFNB3 and shaker 2.
abstract: Mutations in myosin XV are responsible for congenital profound deafness DFNB3 in humans and deafness and vestibular defects in shaker 2 mice. By combining direct cDNA analyses with a comparison of 95.2 kb of genomic DNA sequence from human chromosome 17p11.2 and 88.4 kb from the homologous region on mouse chromosome 11, we have determined the genomic and mRNA structures of the human (MYO15) and mouse (Myo15) myosin XV genes. Our results indicate that full-length myosin XV transcripts contain 66 exons, are >12 kb in length, and encode 365-kDa proteins that are unique among myosins in possessing very long approximately 1200-aa N-terminal extensions preceding their conserved motor domains. The tail regions of the myosin XV proteins contain two MyTH4 domains, two regions with similarity to the membrane attachment FERM domain, and a putative SH3 domain. Northern and dot blot analyses revealed that myosin XV is expressed in the pituitary gland in both humans and mice. Myosin XV transcripts were also observed by in situ hybridization within areas corresponding to the sensory epithelia of the cochlea and vestibular systems in the developing mouse inner ear. Immunostaining of adult mouse organ of Corti revealed that myosin XV protein is concentrated within the cuticular plate and stereocilia of cochlear sensory hair cells. These results indicate a likely role for myosin XV in the formation or maintenance of the unique actin-rich structures of inner ear sensory hair cells.
authors.affiliation: Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH), 5 Research Court, Rockville, Maryland, 20850, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
authors.forename: A
authors.initials: A
authors.lastname: Wang
authors.forename: I A
authors.initials: IA
authors.lastname: Belyantseva
authors.forename: D W
authors.initials: DW
authors.lastname: Anderson
authors.forename: F J
authors.initials: FJ
authors.lastname: Probst
authors.forename: T D
authors.initials: TD
authors.lastname: Barber
authors.forename: W
authors.initials: W
authors.lastname: Miller
authors.forename: J W
authors.initials: JW
authors.lastname: Touchman
authors.forename: L
authors.initials: L
authors.lastname: Jin
authors.forename: S L
authors.initials: SL
authors.lastname: Sullivan
authors.forename: J R
authors.initials: JR
authors.lastname: Sellers
authors.forename: S A
authors.initials: SA
authors.lastname: Camper
authors.forename: R V
authors.initials: RV
authors.lastname: Lloyd
authors.forename: B
authors.initials: B
authors.lastname: Kachar
authors.forename: T B
authors.initials: TB
authors.lastname: Friedman
authors.forename: R A
authors.initials: RA
authors.lastname: Fridell
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003001:Cloning, Molecular; D003051:Cochlea / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D003638:Deafness / Q000151:congenital* / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009218:Myosins / Q000737:chemistry / Q000235:genetics*; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D020080:Tandem Repeat Sequences; D014018:Tissue Distribution; D014158:Transcription, Genetic
chemical_list: D018076:DNA, Complementary; C485245:MYO15A protein, human; C114013:Myo15 protein, mouse; D012333:RNA, Messenger; D009218:Myosins