Open AccessA deletion in a photoreceptor-specific nuclear receptor mRNA causes retinal degeneration in the rd7 mouse
Author(s) -
Novrouz B. Akhmedov,
Natik I. Piriev,
Bo Chang,
Ana Lia Rapoport,
Norman L. Hawes,
Patsy M. Nishina,
Steven Nusinowitz,
John R. Heckenlively,
Thomas H. Roderick,
Christine A. Kozak,
Michael Danciger,
Muriel T. Davisson,
Débora B. Farber
Publication year - 2000
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.97.10.5551
Subject(s) - biology , retinal degeneration , microbiology and biotechnology , retinal , messenger rna , complementary dna , gene , coding region , suppression subtractive hybridization , in situ hybridization , rna , genetics , cdna library , biochemistry
Therd7 mouse, an animal model for hereditary retinal degeneration, has some characteristics similar to human flecked retinal disorders. Here we report the identification of a deletion in a photoreceptor-specific nuclear receptor (mPNR) mRNA that is responsible for hereditary retinal dysplasia and degeneration in therd7 mouse. mPNR was isolated from a pool of photoreceptor-specific cDNAs originally created by subtractive hybridization of mRNAs from normal and photoreceptorlessrd mouse retinas. Localization of the gene corresponding to mPNR to mouse Chr 9 near therd7 locus made it a candidate for the site of therd7 mutation. Northern analysis of total RNA isolated fromrd7 mouse retinas revealed no detectable signal after hybridization with the mPNR cDNA probe. However, with reverse transcription–PCR, we were able to amplify different fragments of mPNR fromrd7 retinal RNA and to sequence them directly. We found a 380-nt deletion in the coding region of therd7 mPNR message that creates a frame shift and produces a premature stop codon. This deletion accounts for more than 32% of the normal protein and eliminates a portion of the DNA-binding domain. In addition, it may result in the rapid degradation of therd7 mPNR message by the nonsense-mediated decay pathway, preventing the synthesis of the corresponding protein. Our findings demonstrate that mPNR expression is critical for the normal development and function of the photoreceptor cells.