Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements.
The trkC gene is expressed throughout the mammalian nervous system and encodes a series of tyrosine protein kinase isoforms that serve as receptors for neurotrophin-3 (NT3), a member of the nerve growth factor (NGF) family of neurotrophic factors. One of these isoforms, gp145trkC/TrkC K1, mediates the trophic properties of NT3 in cultured cells. Here we show that homozygous mice defective for TrkC tyrosine protein kinase receptors lack Ia muscle afferent projections to spinal motor neurons and have fewer large myelinated axons in the dorsal root and posterior columns of the spinal cord. These mice display abnormal movements and postures, indicating that NT3/TrkC-dependent sensor; neurons may play a primary role in proprioception, the sense of position and movement of the limbs.
Klein
R
R
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543.
Silos-Santiago
I
I
Smeyne
R J
RJ
Lira
S A
SA
Brambilla
R
R
Bryant
S
S
Zhang
L
L
Snider
W D
WD
Barbacid
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002452:Cell Count; D002999:Clone Cells; D004247:DNA; D005727:Ganglia, Spinal / Q000473:pathology; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009069:Movement Disorders / Q000235:genetics* / Q000503:physiopathology; D009132:Muscles / Q000294:innervation*; D009154:Mutation; D009475:Neurons, Afferent / Q000473:pathology*; D011187:Posture; D011434:Proprioception / Q000235:genetics; D012326:RNA Splicing; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D020812:Receptor, trkC; D017978:Receptors, Growth Factor / Q000235:genetics / Q000502:physiology*; D013116:Spinal Cord / Q000473:pathology
D017978:Receptors, Growth Factor; D004247:DNA; D020794:Receptor Protein-Tyrosine Kinases; D020812:Receptor, trkC