Deafness and retinal degeneration in a novel USH1C knock‐in mouse model

摘要: Usher syndrome is the leading cause of combined deaf–blindness, but molecular mechanisms underlying auditory and visual impairment are poorly understood. I characterized by profound congenital hearing loss, vestibular dysfunction, progressive retinitis pigmentosa beginning in early adolescence. Using c.216G>A cryptic splice site mutation Exon 3 USH1C gene found Acadian patients Louisiana, we constructed first mouse model that develops both deafness retinal degeneration. The same truncated mRNA transcript 1C cochleae retinas these knock-in mice. Absent auditory-evoked brainstem responses indicated mutant mice deaf at 1 month age. Cochlear histology showed disorganized hair cell rows, abnormal bundles, loss inner outer cells middle turns base. Retinal dysfunction as evident an electroretinogram was seen age, with rod photoreceptors between 6 12 months This reproduces dual sensory human I, providing a novel resource to study disease mechanism development therapies. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 253–267,