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Severe Sensory Deficits but Normal CNS Development in Newborn Mice Lacking TrkB and TrkC Tyrosine Protein Kinase Receptors
Author(s) -
SilosSantiago Inmaculada,
Fagan Anne M.,
Garber Melinda,
Fritzsch Bernd,
Barbacid Mariano
Publication year - 1997
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1997.tb01372.x
Subject(s) - trk receptor , tropomyosin receptor kinase b , tropomyosin receptor kinase c , tropomyosin receptor kinase a , neurotrophin , biology , neuroscience , receptor tyrosine kinase , low affinity nerve growth factor receptor , microbiology and biotechnology , receptor , medicine , endocrinology , neurotrophic factors , signal transduction , genetics , platelet derived growth factor receptor , growth factor
Analysis of mice carrying targeted mutations in genes encoding neurotrophins and their signalling Trk receptors has provided critical information regarding the role that these molecules play in the mammalian nervous system. In this study we generated mice defective in both TrkB and TrkC tyrosine kinase receptors to determine the biological effects of these receptors in the absence of compensatory mechanisms. trk B(–/–); trk C(–/–) double‐mutant mice were born at the expected frequency, indicating that TrkB and TrkC signalling are not required for embryonic survival. However, these double‐mutant mice had a significantly shorter lifespan and displayed more severe sensory defects than their single‐mutant trk B(–/–) and trk C(–/–) littermates. The most dramatic sensory deficit observed in trk B(–/–); trK C(–/–) mutant mice was the absence of vestibular and cochlear ganglia. Interestingly, these mice developed inner ear sensory epithelia in spite of the complete absence of sensory innervation. Analysis of the CNS in trk B(–/–); trk C(–/–) mutant mice revealed a well formed hippocampus, cortex and thalamus. Moreover, the pattern of expression of several neuronal markers appeared normal in these animals. These observations suggest that neurotrophin signalling through TrkB and TrkC receptors is essential for the development of sensory ganglia: however, it does not play a major role in the differentiation and survival of CNS neurons during embryonic development.