Evidence for a role of truncated trkC receptor isoforms in mouse development

The trkC locus encodes several receptors for neurotrophin-3, including the well studied full-length tyrosine kinase isoform, in addition to receptor i soforms lacking the kinase active domain. TrkC receptors are widely express ed throughout mouse development in many different organs. To investigate th e function of truncated receptors in vivo and to identify cell types that a re biologically responsive to this gene product, we have overexpressed a ph ysiological truncated trkC isoform in the mouse. Mice overexpressing this r eceptor develop to term but die in the first postnatal days. High levels of transgene expression result in severe developmental defects in the periphe ral nervous system and in the heart. The severity of neuronal losses observ ed in these animals suggests that truncated receptors may act by sequesteri ng neurotrophin, thus, closely relating this mouse model to the neurotrophi n-3-deficient one. Lower levers of exogenous truncated receptor in transgen ic mice result in a more modest phenotype and, in some neuronal populations , do not cause neural deficits. Taken together, these data suggest that tru ncated trkC receptor isoforms may have modulatory functions in development.