TARGETED DISRUPTION OF THE TRKB NEUROTROPHIN RECEPTOR GENE RESULTS IN NERVOUS-SYSTEM LESIONS AND NEONATAL DEATH

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, trkB(TK) (-/-), develop to birth. However, these animals do not display feeding activity, and most die by P1. Neuroanatomical examination of trkB(TK) (-/-) 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 gp145trkB protein-tyrosine kinase receptor in the ontogeny of the mammalian nervous system.