Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements

@article{Klein1994DisruptionOT,
  title={Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements},
  author={R{\"u}diger Klein and Inmaculada Silos-santiago and Richard J Smeyne and Sergio A. Lira and Riccardo Brambilla and Sherri Bryant and Li Zhang and William Douglas Snider and Mariano Barbacid},
  journal={Nature},
  year={1994},
  volume={368},
  pages={249-251}
}
THE trkC gene1,2 is expressed throughout the mammalian nervous system3-5 and encodes a series of tyrosine protein kinase isoforms that serve as receptors for neurotrophin-3 (NT3), a member of the nerve growth factor (NGF) family of neurotrophic factors2,6–8. One of these isoforms, gp145 trkC /TrkC Kl, mediates the trophic properties of NT3 in cultured cells2,6–8. Here we show that homozygous mice defective for TrkC tyrosine protein kinase receptors lack la muscle afferent projections to spinal… 
Dissection of NT3 functions in vivo by gene replacement strategy.
TLDR
This mouse model has allowed the dissection of specific spatiotemporal Trk receptor activation by NT3 and provides examples of how development can be orchestrated by complex high- and low-affinity interactions between ligand and receptor families.
The Trk family of neurotrophin receptors.
TLDR
Preliminary characterization of these mutant mice has provided significant information regarding the role of these receptors in the ontogeny of the mammalian nervous system, and TrkC-deficient mice display strikingly abnormal movements consistent with loss of proprioception.
Evidence for a Role of Truncated trkC Receptor Isoforms in Mouse Development
TLDR
Data suggest that truncated trkC receptor isoforms may have modulatory functions in development, closely relating this mouse model to the neurotrophin-3-deficient one.
Synchronous Onset of NGF and TrkA Survival Dependence in Developing Dorsal Root Ganglia
TLDR
It is concluded that many murine DRG cells require NT-3 for survival before exhibiting NGF dependence and thatNT-3 activation of TrkA is unimportant to these early NT- 3 survival-promoting actions.
Absence of Sensory Neurons before Target Innervation in Brain-Derived Neurotrophic Factor-, Neurotrophin 3-, and TrkC-Deficient Embryonic Mice
TLDR
It is suggested that neurotrophins may function in creating early heterogeneity that would enable ganglia to compensate for diverse modality requirements before the period of naturally occurring death.
Neurotrophin-3 as an essential signal for the developing nervous system
TLDR
The roles of NT-3 in the nervous system are focused on, which include the essential role in development of specific populations of the PNS, and in particular of proprioceptive, nodose, and auditory sensory neurons and of sympathetic neurons.
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References

SHOWING 1-10 OF 23 REFERENCES
Developmental expression of trkC, the neurotrophin-3 receptor, in the mammalian nervous system
TLDR
The results indicate that the trkC gene is widely expressed in the three identified branches of the mammalian nervous system and appears to correlate with the expression of NT-3, its cognate ligand.
trkC, a receptor for neurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues.
TLDR
Insight is provided into the role of Trk-family receptors and nerve growth factor-related neurotrophins during development and suggest that, in addition to regulating neuronal survival and differentiation, the neurotrophin/Trk receptor system may have broader physiological effects.
Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene
TLDR
These findings demonstrate that Trk is the primary mediator of the trophic actions of NGF in vivo and that this signalling pathway plays a crucial role in the development of both the peripheral and the central nervous systems.
Neurotrophin receptor genes are expressed in distinct patterns in developing dorsal root ganglia
TLDR
It is shown that neurotrophin receptors are expressed in thoracic and lumbar DRGs by embryonic day 13 (E13), which is only 24–48 hr after neurogenesis begins in these ganglia, and trk expression occurs in a time frame consistent with the idea that trks mediate responses of DRG neurons to neurotrophins that are synthesized in both the periphery and spinal cord at early developmental stages.
trkC encodes multiple neurotrophin‐3 receptors with distinct biological properties and substrate specificities.
TLDR
It is reported that trkC encodes at least two additional tyrosine protein kinase receptors that suggest that the trophic activities of NT‐3 in the mammalian nervous system might be mediated by different TrkC receptor isoforms.
Cells Expressing mRNA for Neurotrophins and their Receptors During Embryonic Rat Development
TLDR
In situ hybridization analysis of cells expressing messenger RNAs for the neurotrophins nerve growth factor, brain‐derived neurotrophic factor and neurotrophin‐3 and their high‐affinity receptors in the rat embryo revealed a complex but specific expression pattern for each of these mRNAs, suggesting a broad function in supporting neural innervation during embryonic development.
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