Mouse Model for Usher Syndrome: Linkage Mapping Suggests Homology to Usher Type I Reported at Human Chromosome 11p15

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 92; no. 24; pp. 11100 - 11104
• Main Authors: Heckenlively, John R., Chang, Bo, Erway, Lawrence C., Peng, Chen, Hawes, Norman L., Gregory S.Hageman, Roderick, Thomas H.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 21.11.1995; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Chromosomes; Chromosomes, Human, Pair 11; Deafness - genetics; Deafness - pathology; Deafness - physiopathology; Disease Models, Animal; Ear, Inner - pathology; Genes; Genes, Recessive; Genomics; Hearing loss; Histology; Humans; Mice; Mice, Inbred C57BL; Mice, Mutant Strains - anatomy & histology; Mice, Mutant Strains - genetics; Mice, Mutant Strains - physiology; Outer hair cells; Photoreceptors; Retina; Retinal degeneration; Retinal Degeneration - genetics; Retinal Degeneration - pathology; Retinal Degeneration - physiopathology; Rod Cell Outer Segment - ultrastructure; Syndrome; Usher syndromes
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.24.11100

Usher syndrome is a group of diseases with autosomal recessive inheritance, congenital hearing loss, and the development of retinitis pigmentosa, a progressive retinal degeneration characterized by night blindness and visual field loss over several decades. The causes of Usher syndrome are unknown and no animal models have been available for study. Four human gene sites have been reported, suggesting at least four separate forms of Usher syndrome. We report a mouse model of type I Usher syndrome, rd5, whose linkage on mouse chromosome 7 to Hbb and tub has homology to human Usher I reported on human chromosome 11p15. The electroretinogram in homozygous rd5/rd5 mouse is never normal with reduced amplitudes that extinguish by 6 months. Auditoryevoked response testing demonstrates increased hearing thresholds more than control at 3 weeks of about 30 decibels (dB) that worsen to about 45 dB by 6 months.