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  • N. Held
  • B.M. Smits
  • R. Gockeln
  • S. Schubert
  • H. Nave
  • E. Northrup
  • E. Cuppen
  • H.J. Hedrich
  • D. Wedekind
The LEW/Ztm-ci2 rat is an animal model for syndromal deafness that arose from a spontaneous mutation. Homozygous animals show locomotor abnormalities like lateralized circling behavior. Additionally, an impaired vision can be observed in some animals through behavioral studies. Syndromal deafness as well as retinal degeneration are features of the Usher syndrome in humans. In the present study, the mutation was identified as a base substitution (T->C) in exon 56 of Myo15, leading to an amino acid exchange from leucine (Leu) to proline (Pro) within the carboxy-terminal MyTH4 domain in the proteins' tail region. Myo15 mRNA was expressed in the retina as demonstrated for the first time with the help of in-situ hybridization and PCR. To characterize the visual phenotype, rats were examined by scotopic and photopic electroretinography and, additionally, histological analyses of the retinas were conducted. The complete loss of sight was detected along with a severe degeneration of photoreceptor cells. Interestingly, the manifestation of the disease does not solely depend on the mutation, but also on environmental factors. Since the LEW/Ztm-ci2 rat features the entire range of symptoms of the human Usher syndrome we think that this strain is an appropriate model for this disease. Our findings display that mutations in binding domains of myosin XV do not only cause non-syndromic hearing loss but can also lead to syndromic disorders including retinal dysfunction. [KEYWORDS: Amino Acid Sequence, Animals, Base Sequence, Electroretinography, Environment, Exons/genetics, Female, Gene Expression Regulation/radiation effects, Humans, In Situ Hybridization, Light, Male, Molecular Sequence Data, Mutation/ genetics, Myosins/chemistry/ genetics, Phenotype, RNA, Messenger/genetics/metabolism, Rats, Rats, Mutant Strains, Retinal Degeneration/complications/pathology/physiopathology, Retinal Rod Photoreceptor Cells/physiology/radiation effects, Reverse Transcriptase P
Original languageEnglish
JournalPLoS One
Journal publication date2011

ID: 325758