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Retinopathy induced in mice by targeted disruption of the rhodopsin gene

Nature Genetics volume 15, pages 216–219 (1997)Cite this article

Abstract

Retinitis pigmentosa (RP) represents the most common mendelian degenerative retinopathy of man, involving death of rod photoreceptors, cone cell degeneration, retinal vessel attenuation and pigmentary deposits1,2. The patient experiences night blindness, usually followed by progressive loss of visual field. Genetic linkage between an autosomal dominant RP locus and rhodopsin3, the photoreactive pigment of the rod cells, led to the identification of mutations within the rhodopsin gene in both dominant and recessive forms of RP3–7. To better understand the functional and structural role of rhodopsin in the normal retina and in the pathogenesis of retinal disease, we generated mice carrying a targeted disruption of the rhodopsin gene. Rho−/− mice do not elaborate rod outer segments, losing their photoreceptors over 3 months. There is no rod ERG response in 8-week-old animals. Rho+/− animals retain the majority of their photoreceptors although the inner and outer segments of these cells display some structural disorganization, the outer segments becoming shorter in older mice. These animals should provide a useful genetic background on which to express other mutant opsin transgenes, as well as a model to assess the therapeutic potential of re-introducing functional rhodopsin genes into degenerating retinal tissues.

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Authors and Affiliations

  1. The Wellcome Ocular Genetics Unit, The Genetics Department, Trinity College, Dublin, 2, Ireland

    Marian M. Humphries, G. Jane Farrar, Paul Kenna, Denise M. Sheils, Peter Creighton, Alexandra Erven, Andras Boros & Peter Humphries

  2. Research Foundation, Royal Victoria Eye & Ear Hospital, Adelaide Road, Dublin, 2, Ireland

    Paul Kenna

  3. University of Utah Medical Center, Eccles Institute of Human Genetics, Building 533, Room 5440, Salt Lake City, Utah, 84112, USA

    Derrick Rancourt, Mark Hazel & Mario R. Capecchi

  4. Kellogg Eye Center, University of Michigan, 1000 Wall Street, Ann Arbor, Michigan, USA

    Ronald A. Bush & Paul A. Sieving

  5. University of Szeged, Department of Zoology & Cell Biology, Jozsef Attila University, Egyetem u.2., POB 659, Szeged, H-6722, Hungary

    Karoly Gulya

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  1. Marian M. Humphries
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Humphries, M., Rancourt, D., Farrar, G. et al. Retinopathy induced in mice by targeted disruption of the rhodopsin gene. Nat Genet 15, 216–219 (1997). https://doi.org/10.1038/ng0297-216

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