a mutation in myo15 leads to usher-like symptoms in lewztm-ci2 ratsmyo15的突变导致usher-like症状lewztm-ci2老鼠.pdfVIP

A Mutation in Myo15 Leads to Usher-Like Symptoms in LEW/Ztm-ci2 Rats 1 2 3 4 5 1 Nadine Held , Bart M. G. Smits , Roland Gockeln , Stephanie Schubert , Heike Nave , Emily Northrup , 2 1 1 Edwin Cuppen , Hans J. Hedrich , Dirk Wedekind * 1 Institute of Laboratory Animal Science, Hannover Medical School, Hannover, Germany, 2 Hubrecht Institute, KNAW and University Medical Center Utrecht, Utrecht, The Netherlands, 3 Clinic of Ophthalmology, Hannover Medical School, Hannover, Germany, 4 Institute of Human Genetics, Hannover Medical School, Hannover, Germany, 5 Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany Abstract 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 a