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ZFIN ID: ZDB-PUB-100910-48
Distinct retinal deficits in a zebrafish pyruvate dehydrogenase-deficient mutant
Maurer, C.M., Schönthaler, H.B., Mueller, K.P., and Neuhauss, S.C.
Date: 2010
Source: The Journal of neuroscience : the official journal of the Society for Neuroscience   30(36): 11962-11972 (Journal)
Registered Authors: Neuhauss, Stephan, Schönthaler, Helia Berrit, vom Berg, Colette
Keywords: none
MeSH Terms:
  • Aminobutyrates/pharmacology
  • Analysis of Variance
  • Animals
  • Animals, Genetically Modified
  • Aspartic Acid/pharmacology
  • Choline O-Acetyltransferase/metabolism
  • DNA Mutational Analysis
  • Diet, Ketogenic/methods
  • Disease Models, Animal
  • Electroretinography/methods
  • Embryo, Nonmammalian
  • Excitatory Amino Acid Agonists/pharmacology
  • Larva
  • Movement/physiology
  • Mutation/genetics*
  • Nystagmus, Optokinetic/genetics
  • Nystagmus, Optokinetic/physiology
  • Photic Stimulation/methods
  • Pyruvate Decarboxylase/deficiency*
  • Retina/cytology
  • Retina/embryology
  • Retina/growth & development
  • Retina/pathology
  • Retinal Diseases/diagnosis*
  • Retinal Diseases/diet therapy
  • Retinal Diseases/genetics*
  • Tyrosine 3-Monooxygenase/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics
PubMed: 20826660 Full text @ J. Neurosci.
Mutations in ubiquitously expressed metabolic genes often lead to CNS-specific effects, presumably because of the high metabolic demands of neurons. However, mutations in omnipresent metabolic pathways can conceivably also result in cell type-specific effects because of cell-specific requirements for intermediate products. One such example is the zebrafish noir mutant, which we found to be mutated in the pdhb gene, coding for the E1 β subunit of the pyruvate dehydrogenase complex. This vision mutant is described as blind and was isolated because of its vision defect-related darker appearance. A detailed morphological, behavioral, and physiological analysis of the phenotype revealed an unexpected specific effect on the retina. Surprisingly, the cholinergic amacrine cells of the inner retina are affected earlier than the photoreceptors. This might be attributable to the inability of these cells to maintain production of their neurotransmitter acetylcholine. This is reflected in an earlier loss of motion vision, followed only later by a general loss of light perception. Since both characteristics of the phenotype are attributable to a loss of acetyl-CoA production by pyruvate dehydrogenase, we used a ketogenic diet to bypass this metabolic block and could indeed partially rescue vision and prolong survival of the larvae. The noir mutant provides a case for a systemic disease with ocular manifestation with a surprising specific effect on the retina given the ubiquitous requirement for the mutated gene.