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, trkBTK(-/-), develop to birth. However, these animals do not display feeding activity, and most die by P1. Neuroanatomical examination of trkBTK (-/-) 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.
Klein
R
R
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
Smeyne
R J
RJ
Wurst
W
W
Long
L K
LK
Auerbach
B A
BA
Joyner
A L
AL
Barbacid
M
M
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001755:Blastocyst / Q000502:physiology; D015139:Blotting, Southern; D017931:DNA Primers; D004622:Embryo, Mammalian; D005260:Female; D005727:Ganglia, Spinal / Q000002:abnormalities; D006200:Hair Color / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D007438:Introns; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020801:Receptor, Ciliary Neurotrophic Factor; D020813:Receptor, trkB; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*; D013116:Spinal Cord / Q000002:abnormalities; D013234:Stem Cells / Q000502:physiology; D014162:Transfection
D017931:DNA Primers; D008565:Membrane Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D020813:Receptor, trkB