Gene dosage effect of the TrkB receptor on rod physiology andbiochemistry in juvenile mouse retina

[摘要] Purpose: To strengthen our understanding about the role of trkB inrod development by correlating functional and biochemical retinalphenotypes with levels of trkB expression in two independently createdtrkB transgenic lines.Methods: Juvenile mice that carried two hypomorphic trkB alleles(trkBfbz/fbz) expressing roughly 25% of normal trkB, and theirheterozygous (trkB+/fbz) and wild type (WT) littermates weretested with electroretinographic (ERG) protocols that isolate rod drivenresponses. Rod development was assessed histologically (outer segmentlength) and spectrophotometrically (rhodopsin content). Functional andbiochemical data were compared to those obtained from mice that havetrkB removed completely (trkB-/-).Results: (1) Retinal rod function and morphology was unaffected by aloss of up to 50% of trkB. (2) However, reducing trkB below a criticalthreshold (<50%) significantly reduced rhodopsin content and outersegment length, resulting in reduced a- and b-wave amplitudes and slowerkinetics. (3) A second threshold was determined for rod to bipolar cellsignaling, which requires the presence of at least 25% of wild type trkBlevels.Conclusions: (1) These results demonstrated that rod biochemistry,physiology and synaptic signaling are compromised in a gene dosagedependent manner when the expression of trkB is reduced in transgenicmice. (2) This study confirmed our previous conclusion that the knockoutof trkB expression altered rod development, because this gene product isessential for normal rod maturation and not because of alternativeindirect mechanisms. (3) More generally, this study showed that thespecificity of complex phenotypes can be investigated in gene knockoutmice, if a gene dosage study is performed.

[学科分类] 生物化学/生物物理