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Electroretinography as a Screening Method for Mutations Causing Retinal Dysfunction in Mice

From the GSF-National Research Center for Environment and Health, Institutes of ¹Developmental Genetics, ²Experimental Genetics, and ³Human Genetics and Clinical Cooperation Group Ophthalmogenetics, Neuherberg, Germany; and the ⁴University Eye Hospital, Tübingen, Germany.

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/m² in a pretest series two levels (5 and 125 cd-s/m²) 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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