Usher syndrome is the leading genetic disorder of combined blindness and deafness.
The main clinical symptoms of the disease are retinitis pigmentosa (RP) and hearing
loss. Vestibular dysfunction and mental disturbances are also, in some cases, features of the
syndrome. Usher syndrome is clinically and genetically heterogeneous, and can be divided
into 3 major types. They can be further divided into different genetic sub-types. Mutations
in the myosin VIIa gene (
) cause a major subtype (USH1B) of Usher syndrome. The
shaker1 mouse has mutations in
and is a widely accepted animal model for USH1B.
This mouse model is deaf and shows vestibular dysfunction but does not develop appreciable
photoreceptor degeneration. We provide evidence showing that shaker1 mice have delayed rod
transducin translocation with a shift of its activation threshold. Furthermore, shaker1 is much
more sensitive than strain-matched wild type mice to light-induced photoreceptor damage.
Even moderate light exposure can induce oxidative damage and significant rod degeneration
mice. When shaker1 are reared under moderate light/dark cycle, severe retinal
degeneration develops in less than 6 months. More importantly,
subretinal delivery of EIAV-
based lentiviral vectors expressing human
in the Shaker1 is able to rescue these phenotypes, demonstrating that they result
from lack of myosin VIIa function.
These findings demonstrate that, contrary to earlier studies, shaker-1 mice possess a light-
induced retinal phenotype which is closely related to these defective protein translocations. Importantly USH1B patients are thus
likely vulnerable to light induced photoreceptor damage even under moderate room light.
You-Wei Peng has completed his PhD from Baylor College of Medicine and postdoctoral training from Howard Hughes Medical Institute in Johns Hopkins University. He later joins the faculty of Johns Hopkins University and Duke University. He has published peer-reviewed publications in various well-known journals including Nature , Neuron and PNAS . He is now the director of Retinal Neurobiology Lab in Boys Town National Research Hospital.
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