Electroretinography as a screening method for mutations causing retinal dysfunction in mice.
OBJECTIVE
To detect mice with hereditary retinal impairment, a high-throughput electroretinography (ERG) screening system was established.


METHODS
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.
Dalke
Claudia
C
GSF-National Research Center for Environment and Health, Institutes of. Developmental Genetics, Clinical Cooperation Group Ophthalmogenetics, Neuherberg, Germany.
Löster
Jana
J
Fuchs
Helmut
H
Gailus-Durner
Valerie
V
Soewarto
Dian
D
Favor
Jack
J
Neuhäuser-Klaus
Angelika
A
Pretsch
Walter
W
Gekeler
Florian
F
Shinoda
Kei
K
Zrenner
Eberhart
E
Meitinger
Thomas
T
Hrabé de Angelis
Martin
M
Graw
Jochen
J
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000235:genetics*; D000818:Animals; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D004596:Electroretinography / Q000379:methods*; D005820:Genetic Testing / Q000379:methods; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D009154:Mutation; D016133:Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000175:diagnosis* / Q000235:genetics*
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517438:Pde6b protein, mouse