In vivo role of truncated trkb receptors during sensory ganglion neurogenesis.
The mammalian trkB locus undergoes alternative splicing to produce two different types of brain-derived neurotrophic factor receptors. The first type is the full-length receptor tyrosine kinase (TrkB(Tk+); the second type is a truncated receptor lacking the intracellular tyrosine kinase domain (TrkB(Tk-)). To investigate the function of both types of TrkB receptor in vivo, we have generated knockout mice lacking all isoforms of the TrkB receptor (trkB-/-) and compared sensory neuron survival in these mice to that in the previously described TrkB kinase domain knockout mice (trkB(k)-/-). We observed that the presence of truncated TrkB receptors in trkB(k)-/- mice results in more severe sensory neuron losses. Increased neuron losses associated with the presence of truncated TrkB were most severe in regions where neuron survival is most dependent on brain-derived neurotrophic factor and neurotrophin-3. Our data suggest that truncated TrkB receptors negatively influence neuron survival by interfering with the function of catalytic TrkB receptors.
Luikart
B W
BW
Center for Developmental Biology, Kent Waldrep Foundation, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, 75390-9133, Dallas, TX, USA.
Nef
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S
Shipman
T
T
Parada
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LF
D000818:Animals; D000831:Animals, Newborn; D002232:Carbocyanines; D020134:Catalytic Domain / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics*; D003051:Cochlea / Q000254:growth & development / Q000294:innervation / Q000378:metabolism; D017950:Ganglia, Sensory / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000378:metabolism; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics; D020813:Receptor, trkB / Q000172:deficiency* / Q000235:genetics; D020812:Receptor, trkC / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013136:Spiral Ganglion / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D015996:Survival Rate; D015854:Up-Regulation / Q000235:genetics
C035005:3,3'-dihexadecylindocarbocyanine; D002232:Carbocyanines; D009414:Nerve Growth Factors; D020033:Protein Isoforms; D020813:Receptor, trkB; D020812:Receptor, trkC