Cell
Volume 75, Issue 1, 8 October 1993, Pages 113-122
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Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death

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Summary

We have generated mice carrying a germline mutation in the tyrosine kinase catalytic domain of the trkB gene. This mutation eliminates expression of gp145trkB, a protein-tyrosine kinase that serves as the signaling receptor for two members of the nerve growth factor family of neurotrophins, brain-derived neurotrophic factor and neurotrophin-4. Mice homozygous for this mutation, trkBTK (−l−), develop to birth. However, these animals do not display feeding activity, and most die by P1. Neuroanatomical examination of trkBTK (−l−) mice revealed neuronal deficiencies in the central (facial motor nucleus and spinal cord) and peripheral (trigeminal and dorsal root ganglia) nervous systems. These findings illustrate the role of the gp 145trkB protein-tyrosine kinase receptor in the ontogeny of the mammalian nervous system.

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      Citation Excerpt :

      Many of these factors may exert their action in neuronal polarization by regulating the levels of cAMP and cGMP in developing neurons (Cheng et al., 2011b; Gao et al., 2003; Ming et al., 1997; Nishiyama et al., 2011; Polleux et al., 2000; Shelly et al., 2007, 2010; Szczurkowska et al., 2022; Togashi et al., 2008; Wang and Malbon, 2003). Despite their demonstrated role in neuronal polarization in vitro, no axon/dendrite formation defects were detected in mice with targeted deletion of genes for NGF (Crowley et al., 1994) and BDNF (Jones et al., 1994), or their respective receptors TrkA (Smeyne et al., 1994) and TrkB (Klein et al., 1993). The involvement of multiple factors and their coordinated actions may account for the observations that the disruption of the signaling of a single extracellular cue results in only subtle polarity defects in mammalian neurons in vivo.

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    Present address: Differentiation Program, European Molecular Biology Laboratory, 69012 Heidelberg, Federal Republic of Germany.

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