Ntrk1 (neurotrophic tyrosine kinase, receptor, type 1; also called TrkA) is a receptor for nerve growth factor (Ngf), a neurotrophin which controls aspects of mammalian nervous system development. NGF-NTRK1 (NGF-TrkA) signaling is crucial for the survival and growth of sympathetic neurons as well as small-diameter nociceptive sensory neurons.
These mice carry a floxed F592A mutation in exon 12 of the mouse Ntrk1 gene. The allele is sensitive to a family of small-molecule inhibitors including 1NaPP1 and 1NMPP1 which act selectively, rapidly and reversibly. Without 1NaPP1 or 1NMPP1 application, homozygous mutant mice are hypomorphic, with an approximate 50% reduction of both the number of calcitonin gene-related peptide (CGRP) and Ret-positive neurons in dorsal root ganglion and a reduction of peripheral innervation of both sensory and sympathetic fibers. Although hypomorphic, the mutants are viable and fertile, and signaling is effectively blocked by application of 1NMPP1. In sympathetic neurons cultured from mutant mice, NGF-dependent survival is robustly and specifically blocked by nanomolar concentrations of 1NMPP1 or 1NaPP1. 1NMPP1 application during pregnancy leads loss of superior cervical ganglion neurons. 1NMPP1 treatment during adulthood leads to axon terminal degeneration of a selective group of small-diameter peptidergic sensory neurons.
