Document Detail

Gene dosage effect of the TrkB receptor on rod physiology and biochemistry in juvenile mouse retina.
MedLine Citation:
PMID:  11754334     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To strengthen our understanding about the role of trkB in rod development by correlating functional and biochemical retinal phenotypes with levels of trkB expression in two independently created trkB transgenic lines. METHODS: Juvenile mice that carried two hypomorphic trkB alleles (trkBfbz/fbz) expressing roughly 25% of normal trkB, and their heterozygous (trkB+/fbz) and wild type (WT) littermates were tested with electroretinographic (ERG) protocols that isolate rod driven responses. Rod development was assessed histologically (outer segment length) and spectrophotometrically (rhodopsin content). Functional and biochemical data were compared to those obtained from mice that have trkB removed completely (trkB-/-). RESULTS: (1) Retinal rod function and morphology was unaffected by a loss of up to 50% of trkB. (2) However, reducing trkB below a critical threshold (<50%) significantly reduced rhodopsin content and outer segment length, resulting in reduced a- and b-wave amplitudes and slower kinetics. (3) A second threshold was determined for rod to bipolar cell signaling, which requires the presence of at least 25% of wild type trkB levels. CONCLUSIONS: (1) These results demonstrated that rod biochemistry, physiology and synaptic signaling are compromised in a gene dosage dependent manner when the expression of trkB is reduced in transgenic mice. (2) This study confirmed our previous conclusion that the knockout of trkB expression altered rod development, because this gene product is essential for normal rod maturation and not because of alternative indirect mechanisms. (3) More generally, this study showed that the specificity of complex phenotypes can be investigated in gene knockout mice, if a gene dosage study is performed.
B Rohrer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2001-12-12
Journal Detail:
Title:  Molecular vision     Volume:  7     ISSN:  1090-0535     ISO Abbreviation:  Mol. Vis.     Publication Date:  2001 Dec 
Date Detail:
Created Date:  2001-12-26     Completed Date:  2002-01-10     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9605351     Medline TA:  Mol Vis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  288-96     Citation Subset:  IM    
Storm Eye Institute, Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USA.
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MeSH Terms
Gene Dosage*
Mice, Inbred C57BL
Mice, Inbred ICR
Mice, Knockout
Mice, Transgenic
Photic Stimulation
Receptor, trkB / physiology*
Retina / physiology
Retinal Rod Photoreceptor Cells / physiology*
Rhodopsin / metabolism
Vision, Ocular / physiology
Grant Support
Reg. No./Substance:
9009-81-8/Rhodopsin; EC, trkB

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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