Gene dosage effect of the TrkB receptor on rod physiology and biochemistry in juvenile mouse retina.
OBJECTIVE
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.
Rohrer
B
B
Storm Eye Institute, Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USA. rohrer@musc.edu
D000818:Animals; D004596:Electroretinography; D005260:Female; D018628:Gene Dosage; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010775:Photic Stimulation; D020813:Receptor, trkB / Q000502:physiology*; D012160:Retina / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D012243:Rhodopsin / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology
D012243:Rhodopsin; D020813:Receptor, trkB