Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents.
Neurotrophin-3-deficient (NT-3-deficient) mice were generated by gene targeting. Mutant mice displayed severe movement defects of the limbs, and most died shortly after birth. Substantial portions of peripheral sensory and sympathetic neurons were lost while motor neurons were not affected. Significantly, spinal proprioceptive afferents and their peripheral sense organs (muscle spindles and Golgi tendon organs) were completely absent in homozygous mutant mice. This correlated with a loss of parvalbumin and carbonic anhydrase-positive neurons in the dorsal root ganglion. No gross abnormalities were seen in Pacinian corpuscles, cutaneous afferents containing substance P and calcitonin gene-related peptide, and deep nerve fibers in the joint capsule and tendon. Importantly, the number of muscle spindles in heterozygous mutant mice was half of that in control mice, indicating that NT-3 is present at limiting concentrations in the embryo.
Ernfors
P
P
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Massachusetts 02142.
Lee
K F
KF
Kucera
J
J
Jaenisch
R
R
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D002256:Carbonic Anhydrases / Q000032:analysis; D005314:Embryonic and Fetal Development; D005260:Female; D017950:Ganglia, Sensory / Q000166:cytology; D005728:Ganglia, Sympathetic / Q000166:cytology; D006614:Hindlimb / Q000294:innervation; D008297:Male; D008465:Mechanoreceptors / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D009475:Neurons, Afferent / Q000737:chemistry / Q000166:cytology*; D020933:Neurotrophin 3; D010320:Parvalbumins / Q000032:analysis; D017933:Peripheral Nervous System / Q000196:embryology*; D011434:Proprioception; D013373:Substance P / Q000032:analysis
D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D010320:Parvalbumins; D013373:Substance P; D002256:Carbonic Anhydrases; D015740:Calcitonin Gene-Related Peptide