B6.129S4-Ngfr^tm1Jae/J

Stock number: 002213
Product name: p75^NGFR
Research areas: Apoptosis Research, Neurobiology Research, Sensorineural Research

Description

Mice homozygous for the Ngfr^tm1Jae 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.

Detailed description

Mice homozygous for the Ngfr^tm1Jae 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.

Development

The Ngfr^tm1Jae 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 Ngfr^tm1Jae mutation five or more times to C57BL/6J inbred mice.

Allele

Symbol: Ngfr^tm1Jae
Name: targeted mutation 1, Rudolf Jaenisch
MGI accession ID: MGI:1857226
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ngfr
Marker name: nerve growth factor receptor (TNFR superfamily, member 16)
Chromosome: 11
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.