Targeted disruption of the neurotrophin-3 gene with lacZ induces loss of trkC-positive neurons in sensory ganglia but not in spinal cords.
We have replaced the NT-3 gene with Escherichia coli-derived lacZ gene by means of homologous recombination in embryonic stem cells and thus produced null mutant mice. Mice homozygous for this mutation developed to birth, but most of them could not suck well and died within 2 days after birth. The surviving homozygous mutant mice displayed movement disorder similar to ataxia. The expression of lacZ was widely distributed in the target tissues of peripheral nerves, spinal motor neurons, lumbar dorsal root ganglia and trigeminal ganglia during the prenatal periods. A neuroanatomical examination revealed that there was marked cell reduction present in trigeminal and lumbar dorsal root ganglia in the developing homozygous mutant mice. In these tissues, the expression of trkC, a high-affinity receptor for NT-3, was markedly reduced. In contrast, we did not find any morphological abnormalities, significant cell loss or decreased levels of trkC expression in the motor neurons present in the ventral horn of the spinal cord. These results indicate that the absence of the NT-3 gene leads to a defect in the sensory nervous system, but it may be complemented by other neurotrophins in the motor nervous system during the development.
Tojo
H
H
Discovery Research Laboratories II, Takeda Chemical Industries, Ltd., Osaka, Japan.
Kaisho
Y
Y
Nakata
M
M
Matsuoka
K
K
Kitagawa
M
M
Abe
T
T
Takami
K
K
Yamamoto
M
M
Shino
A
A
Igarashi
K
K
D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D004926:Escherichia coli / Q000235:genetics; D017950:Ganglia, Sensory / Q000473:pathology* / Q000648:ultrastructure; D015870:Gene Expression; D018390:Gene Targeting; D017403:In Situ Hybridization; D051379:Mice; D009414:Nerve Growth Factors / Q000235:genetics*; D020933:Neurotrophin 3; D011995:Recombination, Genetic; D013116:Spinal Cord / Q000473:pathology* / Q000648:ultrastructure; D013234:Stem Cells / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000502:physiology* / Q000648:ultrastructure
D009414:Nerve Growth Factors; D020933:Neurotrophin 3