Mice homozygous for the Ngfrtm1Jae mutation display a decreased cutaneous innervation by calcitonin gene-related peptide- and substance P-immunoreactive sensory fibers. Dorsal root ganglion and superior cervical ganglion neurons deficient in p75 displayed a two- to three-fold decreased sensitivity to nerve growth factor at embryonic day 15 and postnatal day three, respectively.
IMR Colony, The Jackson Laboratory
Mice homozygous for the Ngfrtm1Jae mutation are viable and fertile. They display a decreased cutaneous innervation by calcitonin gene-related peptide- and substance P-immunoreactive sensory fibers. Because of this decreased innervation they develop ulcers on their toes by four months of age. The toes become inflamed and progressively infected. There is also reduced sensitivity to heat in the extremities of these mice. Pineal glands lack sympathetic innervation and innervation to sweat glands on foot pads is either reduced or absent. Deficits in the peripheral nervous system were examined by looking at cellular responses of p75-deficient dorsal root ganglion (DRG) and superior cervical ganglion (SCG) neurons to different neurotrophins. p75-deficient DRG and SCG neurons displayed a two- to three-fold decreased sensitivity to NGF at embryonic day 15 and postnatal day three, respectively. These ages coincide with the peak of naturally occurring cell death. p75-deficient embryonic hippocampal neurons in culture and forebrain neurons in adult mice are resistant to Abeta(1-42) induced neuronal degeneration.
The Ngfrtm1Jae mutant strain was developed in the laboratory of Dr. Rudolf Jaenisch at the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology. The 129/Sv-derived J1 ES cell line was used. The C57BL/6J strain was generated by backcrossing mice carrying the Ngfrtm1Jae mutation five or more times to C57BL/6J inbred mice.
|Allele Name||targeted mutation 1, Rudolf Jaenisch|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Ngfr-; NGFRtm1Jac; p75-; p75(III)-; p75exonIII-; p75NGFR; p75NTR-; p75NTR KO; p75NTRexon3-null; p75e3-; p75-KO; p75NTR-; p75NTR/ExonIII-|
|Gene Symbol and Name||Ngfr, nerve growth factor receptor (TNFR superfamily, member 16)|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin selection cassette was inserted into the third exon of the gene, disrupting the sequences encoding cysteine repeats 2, 3, and 4. Northern blot analysis revealed that the mutant gene did not yield a full length mRNA, however subsequent RT-PCR analysis, described in J:71955, detected an endogenous alternative transcript which lacks exon 3. Western blot analysis showed that the full length isoform was absent in homozygous mutant mice, but an isoform lacking cysteine repeats 2, 3, and 4 was present in both wild and mutant mice. In vitro experiments showed the persisting isoform to be a transmembrane protein that cannot bind neurotrophins but interacts with tyrosine kinase receptors.|
|Mutations Made By|| |
Rudolf Jaenisch, Whitehead Institute, Massachusetts Institute of Technology
When maintaining a live colony, heterozygous mice may be bred together. Although homozygous mice are viable and fertile, recovery of homozygotes is reduced in a heterozygous x heterozygous or heterozygous x homozygous mating. The feet of these mice tend to become sore and to bleed because of the loss of sensory nerves. They need to be handled very carefully to minimize these problems. The lifespan is normal. Expected coat color from breeding is black.
When using the p75NGFR mouse strain in a publication, please cite the originating article(s) and include JAX stock #002213 in your Materials and Methods section.
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