Programm                 "Degeneration und Regeneration– Grundlagen, Diagnostik und Therapie"

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Retinal Degeneration in ClC Chloride Channel Knock-out Mice

Ruether K.
Charité, Dept. of Ophthalmology, Berlin

Purpose: Genetically engineered mouse models, e.g. knock-out (k. o.) mice, are important to understand gene function. The relevance of these mutants for the understanding of retinal physiology and pathophysiology is illustrated by the example of ClC chloride channel ko mice.
Method: ClC-3 und ClC-7 k. o. mouse mutants have been kindly provided by the group of T. Jentsch (Centre for Molecular Neurobiology, Hamburg). The mutants and control mice have been examined by Ganzfeld electroretinography (ERG).
Results: The main phenotypic feature of ClC-3 ko mice is the loss of hippocampus1. The ERG reveals an early retinal degeneration. At postnatal (pn) day 14-15, 1-2 days after eye opening, no ERG responses were recordable. In a subset of mutant mice, a shallow negativ potential could be observed. The ClC7-ko mouse model is characterized by osteopetrosis (2). Again, the ERG shows a retinal degeneration, but slower than in ClC-3 ko. At pn day 29 only rest potentials were recordable. The ERG argues for a primary retinal degeneration. There was no hint for a secondary retinal degeneration due to osteopetrosis.
Conclusions: The investigation of retinal function in genetically engineered mouse models lead to a better understanding of retinal physiology and pathophysiology. In addition, retinal function is essential for the characterization of the phenotype of mutants with potenial impact on the central nervous system.
(1) Stobrawa SM, Breiderhof

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