title: The Time Course of Deafness and Retinal Degeneration in a Kunming Mouse Model for Usher Syndrome.
abstract: Usher syndrome is a group of autosomal recessive diseases characterized by congenital deafness and retinitis pigmentosa. In a mouse model for Usher syndrome, KMush/ush, discovered in our laboratory, we measured the phenotypes, characterized the architecture and morphology of the retina, and quantified the level of expression of pde6b and ush2a between postnatal (P) days 7, and 56. Electroretinograms and auditory brainstem response were used to measure visual and auditory phenotypes. Fundus photography and light microscopy were used to measure the architecture and morphology of the retina. Quantitative real-time PCR was used to measure the expression levels of mRNA. KMush/ush mice had low amplitudes and no obvious waveforms of Electroretinograms after P14 compared with controls. Thresholds of auditory brainstem response in our model were higher than those of controls after P14. By P21, the retinal vessels of KMush/ush mice were attenuated and their optic discs had a waxy pallor. The retinas of KMush/ush mice atrophied and the choroidal vessels were clearly visible. Notably, the architecture of each retinal layer was not different as compared with control mice at P7, while the outer nuclear layer (ONL) and other retinal layers of KMush/ush mice were attenuated significantly between P14 and P21. ONL cells were barely seen in KMush/ush mice at P56. As compared with control mice, the expression of pde6b and ush2a in KMush/ush mice declined significantly after P7. This study is a first step toward characterizing the progression of disease in our mouse model. Future studies using this model may provide insights about the etiology of the disease and the relationships between genotypes and phenotypes providing a valuable resource that could contribute to the foundation of knowledge necessary to develop therapies to prevent the retinal degeneration in patients with Usher Syndrome.
authors.affiliation: Department of Clinical Aerospace Medicine, Fourth Military Medical University, 169 West Changle Road, Xi'an, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yao
authors.affiliation: Department of Clinical Aerospace Medicine, Fourth Military Medical University, 169 West Changle Road, Xi'an, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Physical Examination, Air Force General Hospital, 30 Fucheng Road, Beijing, China.
authors.forename: Lin-Song
authors.initials: LS
authors.lastname: Qi
authors.affiliation: Medical Experiment Center, Shaanxi University of Chinese Medicine, Shiji Ave., Xi'an-Xianyang New Ecomic Zone, 712046, Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Clinical Aerospace Medicine, Fourth Military Medical University, 169 West Changle Road, Xi'an, China.
authors.forename: Jing
authors.initials: J
authors.lastname: An
authors.affiliation: Department of Clinical Aerospace Medicine, Fourth Military Medical University, 169 West Changle Road, Xi'an, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Clinical Aerospace Medicine, Fourth Military Medical University, 169 West Changle Road, Xi'an, China.
authors.forename: Jun-Hui
authors.initials: JH
authors.lastname: Xue
authors.affiliation: Department of Clinical Aerospace Medicine, Fourth Military Medical University, 169 West Changle Road, Xi'an, China.
authors.forename: Zuo-Ming
authors.initials: ZM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics; D003638:Deafness / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D004596:Electroretinography; D016057:Evoked Potentials, Auditory, Brain Stem; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D005654:Fundus Oculi; D008297:Male; D051379:Mice; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D052245:Usher Syndromes / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*
chemical_list: D016326:Extracellular Matrix Proteins; C491810:Ush2a protein, mouse; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517438:Pde6b protein, mouse