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PubMed · 14744904

Electroretinography as a screening method for mutations causing retinal dysfunction in mice.

Claudia Dalke·Jana Löster·Helmut Fuchs·Valerie Gailus-Durner·Dian Soewarto·Jack Favor·Angelika Neuhäuser-Klaus·Walter Pretsch·Florian Gekeler·Kei Shinoda·Eberhart Zrenner·Thomas Meitinger·Martin Hrabé de Angelis·Jochen Graw
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Abstract

PURPOSE: To detect mice with hereditary retinal impairment, a high-throughput electroretinography (ERG) screening system was established. METHOD: Mice from eight different strains without known retinal disorders (102, 129/SvJ, AKR, C57BL/6J, C57BL/6JIco, CBA/CaJ, and DBA/2NCrlBR) and one control strain with retinal degeneration (C3HeB/FeJ) were fixed on a specially constructed sled, ERG electrodes were placed on the cornea, and mice were moved into a Ganzfeld stimulator. From a luminance range of 0.0125 to 500 cd-s/m(2) in a pretest series two levels (5 and 125 cd-s/m(2)) were chosen to shorten examination times. The root mean square (RMS) of the ERG-recording was analyzed to detect animals with abnormal retinal function. ERG responses of the left and right eyes were compared in amplitudes and implicit times of the a- and b-waves. Statistical analysis of the latter parameters was performed in all wild-type animals. Histology was performed on selected mice. RESULTS: ERG recordings of individual animals for the left and right eye revealed good agreement in amplitudes and implicit times of the a- and b-waves (P < 0.05). Comparison of these parameters among the wild-type strains showed several differences. Evaluation of the RMS revealed, in addition to the C3HeB/FeJ mice, a subgroup of mice within the 129/SvJ strain with abnormal retinal function. Molecular analysis of these mice demonstrated the presence of the same retroviral insertion in the Pde6b gene, which is causative of the Pde6b(rd1) allele carried in C3HeB/FeJ mice. Histologic analysis demonstrated good correlation between retinal electrophysiology and morphology. CONCLUSIONS: The present results demonstrate the feasibility of ERG for screening a large number of mice to detect animals with functional retinal impairment.

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3',5'-Cyclic-GMP PhosphodiesterasesAnimalsCyclic Nucleotide Phosphodiesterases, Type 6DNA Mutational AnalysisDisease Models, AnimalElectroretinographyGenetic TestingMiceMice, Inbred AKRMice, Inbred C3HMice, Inbred C57BLMice, Inbred CBAMice, Inbred DBAMice, Mutant StrainsMutationPolymerase Chain ReactionRetinal DegenerationJournal ArticleResearch Support, Non-U.S. Gov't

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Claudia Dalke, Jana Löster, Helmut Fuchs, Valerie Gailus-Durner, Dian Soewarto, Jack Favor, Angelika Neuhäuser-Klaus, Walter Pretsch, Florian Gekeler, Kei Shinoda, Eberhart Zrenner, Thomas Meitinger, Martin Hrabé de Angelis, Jochen Graw. 2004. Electroretinography as a screening method for mutations causing retinal dysfunction in mice.. https://doi.org/10.1167/iovs.03-0561

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