SEVERE SENSORY DEFICITS BUT NORMAL CNS DEVELOPMENT IN NEWBORN MICE LACKING TRKB AND TRKC TYROSINE PROTEIN-KINASE RECEPTORS

Analysis of mice carrying targeted mutations in genes encoding neurotr ophins and their signalling Trk receptors has provided critical inform ation regarding the role that these molecules play in the mammalian ne rvous system. In this study we generated mice defective in both TrkB a nd TrkC tyrosine kinase receptors to determine the biological effects of these receptors in the absence of compensatory mechanisms. trkB(-/- );trkC(-/-) double-mutant mice were born at the expected frequency, in dicating that TrkB and TrkC signalling are not required for embryonic survival. However, these double-mutant mice had a significantly shorte r lifespan and displayed more severe sensory defects than their single -mutant trkB(-/-) and trkC(-/-) littermates. The most dramatic sensory deficit observed in trkB(-/-);trkC(-/-) mutant mice was the absence o f vestibular and cochlear ganglia. Interestingly, these mice developed inner ear sensory epithelia in spite of the complete absence of senso ry innervation. Analysis of the CNS in trkB(-/-);trkC(-/-) mutant mice revealed a well formed hippocampus, cortex and thalamus. Moreover, th e pattern of expression of several neuronal markers appeared normal in these animals. These observations suggest that neurotrophin signallin g through TrkB and TrkC receptors is essential for the development of sensory ganglia; however, it does not play a major role in the differe ntiation and survival of CNS neurons during embryonic development.