Overview

Also Known As:p75^NGFR

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.

Donating Investigator

IMR Colony, The Jackson Laboratory

Genetic overview

Genetic Background	Generation
000664 C57BL/6J

Ngfr^tm1Jae

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ngfr	nerve growth factor receptor (TNFR superfamily, member 16)

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Research Applications

Neurobiology Research
Sensorineural Research
Apoptosis Research

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Base Price

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$2,854.50 Domestic price Cryo Recovery

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Details

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.

Control Suggestions

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Lee KF; Li E; Huber LJ; Landis SC; Sharpe AH; Chao MV; Jaenisch R. 1992. Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system. Cell 69(5):737-49PubMed: 1317267 MGI: J:43748

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Genetics

Ngfr^tm1Jae

Allele Symbol: Ngfr^tm1Jae

Allele Name	targeted mutation 1, Rudolf Jaenisch
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Ngfr^-; NGFR^tm1Jac; p75-; p75(III)^-; p75^exonIII-; p75^NGFR; p75^NTR-; p75^NTR KO; p75^NTRexon3-null; p75e3-; p75-KO; p75NTR-; p75NTR/ExonIII-
Gene Symbol and Name	Ngfr, nerve growth factor receptor (TNFR superfamily, member 16)
Gene Synonym(s)
Strain of Origin	129S4/SvJae
Chromosome	11
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

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Neurobiology Research
- Alzheimer's Disease
Sensorineural Research
- Nociception

Genotype: Ngfr^tm1Jae related

Apoptosis Research
- Death Receptors
Neurobiology Research
- Neurotrophic Factor Defects
- Receptor Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
C;129S-Ngfr/J

cellular phenotype

abnormal neuron apoptosis
- reduced levels of neuronal cell death

nervous system phenotype

abnormal neuron apoptosis
- reduced levels of neuronal cell death

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
involves: 129S1/Sv * 129S4/SvJae

nervous system phenotype

abnormal retinal ganglion cell morphology
- the nasal domain of retinal axon termination zone is expanded anteriorly and in some cases evidence of ectopic arborization in non-labelled axons unlike in wild-type mice
- at P8, the termination zone of retinal ganglion cell axons in the superior colliculus is shifted anteriorly compared to in wild-type mice

abnormal superior colliculus morphology
- at P8, the termination zone of retinal ganglion cell axons in the superior colliculus is shifted anteriorly compared to in wild-type mice
- the nasal domain of retinal axon termination zone is expanded anteriorly and in some cases evidence of ectopic arborization in non-labelled axons unlike in wild-type mice

vision/eye phenotype

abnormal retinal ganglion cell morphology
- the nasal domain of retinal axon termination zone is expanded anteriorly and in some cases evidence of ectopic arborization in non-labelled axons unlike in wild-type mice
- at P8, the termination zone of retinal ganglion cell axons in the superior colliculus is shifted anteriorly compared to in wild-type mice

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
involves: 129S4/SvJae * C57BL/6

nervous system phenotype

abnormal axon pruning
- SCG neurons in wild-type mice reduce through axon pruning the number of neurons projecting to both eyes from 78% at p20 to 20% at p50
- sympathetic neurons of the superior cervical ganglion (SCG) have improper pruning of axons from neurons that reach into both eye compartments
- mutant mice have a similar percentage of SCG neurons that connect to both eyes at P20 but this percentage does not decrease with age
- at p35 where SCG neurons are actively pruning exons in wild-type mice, mutant mice have significantly less degenerating SCG axons than in wild-type mice

abnormal axon extension
- axons of mutant neurons grown in vitro in the presence of NGF grow equally well regardless if they are stimulated or not in contrast to wild-type neurons where stimulated axons out compete non-stimulated axons
- this lack of growth disadvantage in non-stimulated axons is due to less axon degeneration than occurs to wild-type neurons

cellular phenotype

abnormal axon pruning
- at p35 where SCG neurons are actively pruning exons in wild-type mice, mutant mice have significantly less degenerating SCG axons than in wild-type mice
- sympathetic neurons of the superior cervical ganglion (SCG) have improper pruning of axons from neurons that reach into both eye compartments
- mutant mice have a similar percentage of SCG neurons that connect to both eyes at P20 but this percentage does not decrease with age
- SCG neurons in wild-type mice reduce through axon pruning the number of neurons projecting to both eyes from 78% at p20 to 20% at p50

abnormal axon extension
- this lack of growth disadvantage in non-stimulated axons is due to less axon degeneration than occurs to wild-type neurons
- axons of mutant neurons grown in vitro in the presence of NGF grow equally well regardless if they are stimulated or not in contrast to wild-type neurons where stimulated axons out compete non-stimulated axons

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
involves: 129S4/SvJae * BALB/c

behavior/neurological phenotype

abnormal sensory capabilities/reflexes/nociception
- prolonged latency in hot plate test

homeostasis/metabolism phenotype

extremity edema
- at 4 months of age, mice exbihit edema in the fore- and hindlimb paws

integument phenotype

absent hair follicles
- loss of follicles, at distal extremities, progressive to more proximal regions

limbs/digits/tail phenotype

ulcerated paws
- epidermis and epidermal structures are lost from areas affected by ulcers
- ulcers are complicated by secondary infections that result in the lose of toenails and hair
- at 4 months of age, fore- and hindlimb paws become edematous and develop severe ulcers
- excessive epidermal proliferation is present at the edges of ulcers
- ulcers progress more proximally

mammalian phenotype

renal/urinary system phenotype
- Normal - unlike in studies using p75^NGFR oligonucleotide knockdown, kidney function is normal

muscle phenotype

abnormal muscle morphology
- muscles exhibit fewer myelinated fibers than in wild-type mice (36+/-2 compared to 76+/-2 in wild-type mice)

decreased muscle spindle number
- spindle density in the soleus, but no the medial gastrocnemius, plantaris and lumbrical muscles, is reduced 50% compared to in wild-type mice

nervous system phenotype

abnormal sensory neuron innervation pattern
- reduced innervation is not restricted to hairless patches
- at 3 to 5 months, Pde6a+ pulpal neurons are decreased
- only a few single fibers are present in the subepidermis and none are detected in the epidermis of fore- and hindlimb paws
- the dermis of fore- and hindlimb paws either lacks or have reduced numbers of Pde6a+ sensory fibers and small-diameter nerves are absent
- Normal - however, sympathetic innervation of the iris and salivary glands is normal

abnormal dorsal root ganglion morphology
- mice exhibit a loss of myelinated fibers in the dorsal root ganglion

small L4 dorsal root ganglion
- at E14.5, L4 is smaller than in wild-type mice due to a 7.5-fold increase in apoptosis

abnormal proprioceptive neuron morphology
- mice exhibit a 50% loss of proprioreceptive neurons in L4 of the dorsal root ganglion

decreased muscle spindle number
- spindle density in the soleus, but no the medial gastrocnemius, plantaris and lumbrical muscles, is reduced 50% compared to in wild-type mice

skeleton phenotype

abnormal tooth morphology
- increased signs of wear on molars

abnormal molar crown morphology
- maxillary molar crown height is reduced by 15%
- Normal - however, full height of teeth is normal

abnormal molar morphology
- mandibular molar occlusal facets are longer than in wild-type mice

craniofacial phenotype

abnormal molar morphology
- mandibular molar occlusal facets are longer than in wild-type mice

abnormal mouth morphology
- the height of the oral cavity is reduced

abnormal molar crown morphology
- maxillary molar crown height is reduced by 15%
- Normal - however, full height of teeth is normal

abnormal tooth morphology
- increased signs of wear on molars

growth/size/body region phenotype

abnormal molar crown morphology
- Normal - however, full height of teeth is normal
- maxillary molar crown height is reduced by 15%

abnormal mouth morphology
- the height of the oral cavity is reduced

abnormal tooth morphology
- increased signs of wear on molars

abnormal molar morphology
- mandibular molar occlusal facets are longer than in wild-type mice

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
involves: 129S4/SvJae

behavior/neurological phenotype

abnormal spatial learning
- spatial learning is improved compared to in wild-type mice without deterioration with age

nervous system phenotype

abnormal retinal ganglion cell morphology
- at P8, the termination zone of retinal ganglion cell axons in the superior colliculus is shifted anteriorly compared to in wild-type mice
- the nasal domain of retinal axon termination zone is expanded anteriorly and in some cases evidence of ectopic arborization in non-labelled axons unlike in wild-type mice
- 50% of mice exhibit ectopic branches and arbors along the anterior posterior length of the nasal RGC axons in the superior colliculus unlike in wild-type mice

decreased neuron apoptosis
- at E12 and E14, neuron apoptosis is reduced 72% and 70%, respectively, compared to in wild-type mice
- nearly all neurons cultured with NT4 survive unlike wild-type neurons

abnormal superior colliculus morphology
- Normal - however, total area of the superior colliculus is normal
- at P8, the termination zone of retinal ganglion cell axons in the superior colliculus is shifted anteriorly compared to in wild-type mice
- the nasal domain of retinal axon termination zone is expanded anteriorly and in some cases evidence of ectopic arborization in non-labelled axons unlike in wild-type mice

abnormal axon guidance
- Normal - however, avoidance of stripes with EPHA5-Fc is normal
- when given the choice between strips that contain Eph47-Fc or Fc, retinal axons fail to avoid EPHA7-Fc stripes or exhibit a preference for the Fc stripes unlike wild-type axons

abnormal sensory neuron innervation pattern
- absence of sensory innervation to pineal and sweat glands

abnormal cholinergic neuron morphology
- increased size of cholinergic forebrain neurons

abnormal trigeminal ganglion morphology
- ophthalmic branch of the trigeminal ganglion is severely truncated at E12.5

cellular phenotype

abnormal axon guidance
- Normal - however, avoidance of stripes with EPHA5-Fc is normal
- when given the choice between strips that contain Eph47-Fc or Fc, retinal axons fail to avoid EPHA7-Fc stripes or exhibit a preference for the Fc stripes unlike wild-type axons

decreased neuron apoptosis
- at E12 and E14, neuron apoptosis is reduced 72% and 70%, respectively, compared to in wild-type mice
- nearly all neurons cultured with NT4 survive unlike wild-type neurons

vision/eye phenotype

abnormal retinal ganglion cell morphology
- the nasal domain of retinal axon termination zone is expanded anteriorly and in some cases evidence of ectopic arborization in non-labelled axons unlike in wild-type mice
- 50% of mice exhibit ectopic branches and arbors along the anterior posterior length of the nasal RGC axons in the superior colliculus unlike in wild-type mice
- at P8, the termination zone of retinal ganglion cell axons in the superior colliculus is shifted anteriorly compared to in wild-type mice

abnormal eye physiology
- mice subjected to intraocular injection of the pro form of nerve growth factor are protected from induced retinal ganglion cell death

homeostasis/metabolism phenotype

abnormal tumor necrosis factor level
- the pro form of nerve growth factor fails to induce TNF expression in retinas

immune system phenotype

abnormal tumor necrosis factor level
- the pro form of nerve growth factor fails to induce TNF expression in retinas

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
involves: 129 * BALB/c

cellular phenotype

abnormal axon extension
- reduced inhibition by myelin of neurite outgrowth from dorsal root ganglion neurons, but not cerebellar neurons, compared to heterozygous controls, indicating that mutant neurons are much less sensitive to myelin
- reduced inhibition by Nogo-66 (Rtn4) peptide of neurite outgrowth from P7 cerebellar neurons compared with heterozygous controls, however homozygotes did not show enhanced regeneration of corticospinal tract axons in comparison with wild-type after spinal dorsal hemisection
- dorsal hemisection

nervous system phenotype

abnormal axon extension
- dorsal hemisection
- reduced inhibition by myelin of neurite outgrowth from dorsal root ganglion neurons, but not cerebellar neurons, compared to heterozygous controls, indicating that mutant neurons are much less sensitive to myelin
- reduced inhibition by Nogo-66 (Rtn4) peptide of neurite outgrowth from P7 cerebellar neurons compared with heterozygous controls, however homozygotes did not show enhanced regeneration of corticospinal tract axons in comparison with wild-type after spinal dorsal hemisection

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
involves: 129S4/SvJae * C57BL/6J

nervous system phenotype

decreased motor neuron number
- the number of motor neurons in tibial nerve is reduced

abnormal peripheral nervous system regeneration
- motor axonal regeneration is increased in the tibial nerve cross-suture

The following phenotype relates to a compound genotype created using this strain

Genotype: Ngfr^tm1Jae/Ngfr⁺
B6.129S4-Ngfr

cellular phenotype

abnormal axon extension
- neurons exhibit an intermediate effect to Sema3a repulsion that is more sensitive than wild-type neurons but not as sensitive as Ngfr^tm1Jae homozygotes

abnormal neuron differentiation
- nerve coverage is less than in wild-type mice but not as severely reduced as in Ngfr^tm1Jae homozygotes

respiratory system phenotype

decreased airway responsiveness
- unlike in wild-type mice, no airway hyper-responsiveness was observed following exposure to Ach and ovalbumin (50% brionchiorestriction occurs at 580 ug per kg for Ach and 586 ug per kg ovalbulmin compared to 552 ug per kg Ach and 62.5 ug per kg ovalbumin for wild-type mice)
- unlike in exposed wild-type mice IL-4 and IL-5 production is not increased
- while IgE levels increase following exposure to provocation they do not increase as much as in wild-type mice
- unlike in exposed wild-type mice, no pulmonary eosinophilic inflammation is observed
- for wild-type mice)
- Normal - however, interferon-gamma production following exposure to provocation agent is normal
- total leukocytes, eosinophils and lymphocytes do not increase as in wild-type following exposure to provocation agent

nervous system phenotype

abnormal axon extension
- neurons exhibit an intermediate effect to Sema3a repulsion that is more sensitive than wild-type neurons but not as sensitive as Ngfr^tm1Jae homozygotes

abnormal neuron differentiation
- nerve coverage is less than in wild-type mice but not as severely reduced as in Ngfr^tm1Jae homozygotes

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
B6.129S4-Ngfr

craniofacial phenotype

abnormal circumvallate papillae morphology
- the vallate papilla is deformed and small in neonatal mutants
- at P7 the vallate trench is only 60% as deep as in wild-type mice

abnormal tongue epithelium morphology
- at P7 the gustatory epithelium of the vallate trench is thicker than normal blocking direct access of the ectopic tastse buds in the trench to taste solutions

digestive/alimentary phenotype

abnormal tongue epithelium morphology
- at P7 the gustatory epithelium of the vallate trench is thicker than normal blocking direct access of the ectopic tastse buds in the trench to taste solutions

abnormal circumvallate papillae morphology
- at P7 the vallate trench is only 60% as deep as in wild-type mice
- the vallate papilla is deformed and small in neonatal mutants

growth/size/body region phenotype

abnormal circumvallate papillae morphology
- at P7 the vallate trench is only 60% as deep as in wild-type mice
- the vallate papilla is deformed and small in neonatal mutants

abnormal tongue epithelium morphology
- at P7 the gustatory epithelium of the vallate trench is thicker than normal blocking direct access of the ectopic tastse buds in the trench to taste solutions

hematopoietic system phenotype

abnormal Kupffer cell morphology
- after 3 weeks in culture hepatic stellate cells are in a quiescent state and are less differentiated than in wild-type mice

cardiovascular system phenotype

abnormal vascular wound healing
- apoptosis in neointimal lesions is decreased by 60% to 70%
- Normal - however, infiltration of inflammatory cells is normal
- formation of neointimal lesions is enhanced 2 and 4 weeks after ligation compared to in wild-type mice such that there is a 2- to 4-fold increase in intimal to medial ratio at 500 um and 1.0 mm proximal to the ligation

abnormal Kupffer cell morphology
- after 3 weeks in culture hepatic stellate cells are in a quiescent state and are less differentiated than in wild-type mice

homeostasis/metabolism phenotype

abnormal vascular wound healing
- Normal - however, infiltration of inflammatory cells is normal
- formation of neointimal lesions is enhanced 2 and 4 weeks after ligation compared to in wild-type mice such that there is a 2- to 4-fold increase in intimal to medial ratio at 500 um and 1.0 mm proximal to the ligation
- apoptosis in neointimal lesions is decreased by 60% to 70%

immune system phenotype

increased susceptibility to experimental autoimmune encephalomyelitis
- mice display considerable infiltration of fibronectin into the spinal cord parenchyma
- B220+ B cells make up 6% of cells in the inflammatory cuffs compared to 15% in wild-type mice immunized with MOG35-55
- Normal - however, the number of double-positive (monocyte) cells is normal
- mice have an increased risk of developing severe experimental autoimmune encephalomyelitis compared to wild-type mice
- microglial/macrophage and neutrophil numbers in the inflammatory infiltrate are reduced 68% to 40% while the size of the inflitratory cuffs is normal or even larger than in wild-type mice
- polymorphonuclear cells are reduced by half compared to in wild-type mice immunized with MOG35-55
- the population of Iba-1+ cells in the inflammatory cuffs is reduced by 10% compared to in wild-type mice immunized with MOG35-55

abnormal Kupffer cell morphology
- after 3 weeks in culture hepatic stellate cells are in a quiescent state and are less differentiated than in wild-type mice

liver/biliary system phenotype

abnormal Kupffer cell morphology
- after 3 weeks in culture hepatic stellate cells are in a quiescent state and are less differentiated than in wild-type mice

nervous system phenotype

abnormal neuron differentiation
- peripheral nerves in the hindlimb, forelimb, and trigeminal ganglia are severely stunted compared to in wild-type mice

abnormal sensory neuron innervation pattern
- at P0 there are 35% fewer geniculate ganglion neurons that supply taste neurons to the fungiform papillae in homozygotes compared to wild-type mice
- innervation of the somatosensory prominences is reduced
- innervation of the fungiform papillae are reduced

abnormal neuron morphology
- at 60 weeks sympathetic neuron cell bodies are 25% smaller than in wild-type mice
- like wild-type neurons, cultured superior cervical ganglion neurons are resistant to apoptosis induced by pro-NGF and pro-BDNF
- the number of sympathetic neurons is increased 33% at P4 and 39% at P15 compared to in wild-type mice
- unlike in wild-type mice, superior cervical ganglion are protected from age-related apoptosis

abnormal innervation pattern to muscle
- areas of the epithelium of the tongue lack innervation and the filiform papillae are sparsely innervated
- the axons in the tongue display reduced branching and smaller terminal arbors

increased retinal photoreceptor cell number
- after 2 weeks of light exposure, the number of rows of photoreceptors is 4.6+/-0.31 rows compared to 2.3+/-0.25 in wild-type mice and 21.2+/-0.25 in homozygous mice
- after 3 weeks of light exposure, the number of rows of photoreceptors is 3.0+/-0.41 rows compared to 1.5+/-0.24 in wild-type mice and 0.9+/-0.28 in homozygous mice

increased neuron number
- the number of sympathetic neurons is increased 33% at P4 and 39% at P15 compared to in wild-type mice

abnormal axon extension
- growth cones from dorsal root ganglion neurons are more sensitive to Sema3A repulsion than wild-type neurons
- Normal - however, increased sensitivity to Sema3A repulsion is alleviated in a double heterozygote cross of Ngfr and Sema3A
- when treated with 15 pM Sema3A outgrowth rate inhibition is increased (15 um per hour compared to 35 um per hour for wild-type neurons)

taste/olfaction phenotype

abnormal gustatory papillae taste bud morphology
- homozygous mice have fewer fungiform taste buds than wild-type mice
- at P7 homozygous mice have 26% fewer vallate taste buds than wild-type mice

cellular phenotype

abnormal axon extension
- growth cones from dorsal root ganglion neurons are more sensitive to Sema3A repulsion than wild-type neurons
- Normal - however, increased sensitivity to Sema3A repulsion is alleviated in a double heterozygote cross of Ngfr and Sema3A
- when treated with 15 pM Sema3A outgrowth rate inhibition is increased (15 um per hour compared to 35 um per hour for wild-type neurons)

abnormal neuron differentiation
- peripheral nerves in the hindlimb, forelimb, and trigeminal ganglia are severely stunted compared to in wild-type mice

vision/eye phenotype

increased retinal photoreceptor cell number
- after 3 weeks of light exposure, the number of rows of photoreceptors is 3.0+/-0.41 rows compared to 1.5+/-0.24 in wild-type mice and 0.9+/-0.28 in homozygous mice
- after 2 weeks of light exposure, the number of rows of photoreceptors is 4.6+/-0.31 rows compared to 2.3+/-0.25 in wild-type mice and 21.2+/-0.25 in homozygous mice

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
B6.129S4-Ngfr/J

cardiovascular system phenotype

decreased myocardial infarct size
- 10 days after myocardial ischemic/reperfusion injury

homeostasis/metabolism phenotype

decreased myocardial infarct size
- 10 days after myocardial ischemic/reperfusion injury

nervous system phenotype

cochlear ganglion degeneration
- starting at 1 month, male homozygotes show a slight (15.7%) but progressive loss of SGNs from the basal to the apical cochlear turns
- at 4 months, male homozygotes display significant SGN degeneration in the basal cochlear turn and swelling of the afferent dendrites below IHCs in the middle turns
- by 6 months, the density of SGNs is significantly reduced in the middle and basal turns, with a 59.8% loss of SGNs in the most basal turns

cochlear hair cell degeneration
- by 6 months, male homozygotes exhibit absence or damage of cochlear HCs in both the basal and upper turns
- Normal - however, IHCs are still present and morphologically normal at 4 months, suggesting that SGN's dendrites connecting the IHCs are damaged earlier than IHCs

hearing/vestibular/ear phenotype

increased susceptibility to age-related hearing loss
- by 1 year of age, homozygotes are unresponsive to click stimuli at the maximum level (136 dB SPL)
- starting at 4 months, male homozygotes display an age-related progressive hearing loss relative to age-matched wild-type males

organ of Corti degeneration
- by 6 months, male homozygotes show complete degeneration of the organ of Corti in the basal turns
- at 1 month of age, male homozygotes exhibit a grossly normal organ of the Corti, except for a slight reduction in the number of SGNs

cochlear hair cell degeneration
- by 6 months, male homozygotes exhibit absence or damage of cochlear HCs in both the basal and upper turns
- Normal - however, IHCs are still present and morphologically normal at 4 months, suggesting that SGN's dendrites connecting the IHCs are damaged earlier than IHCs

increased or absent threshold for auditory brainstem response
- at 6 months and 1 year, male homozygotes continue to display significant increases in ABR thresholds relative to age-matched wild-type males (100 and 126 dB SPL, respectively)
- at 4 months of age, male homozygotes exhibit a significant elevation (>33 dB SPL) in click-evoked ABR thresholds relative to wild-type males
- however, no significant differences in click-evoked ABR thresholds are observed at 1 month, consistent with a normal cochlear structure at this age

sensorineural hearing loss
- male homozygotes show progressive hearing loss at 4 months, when both SGN degeneration and hair cell loss are observed in the basal cochlear turn

References

Lee KF; Li E; Huber LJ; Landis SC; Sharpe AH; Chao MV; Jaenisch R. 1992. Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system. Cell 69(5):737-49PubMed: 1317267 MGI: J:43748

Additional References

Carter AR; Berry EM; Segal RA. 2003. Regional expression of p75NTR contributes to neurotrophin regulation of cerebellar patterning. Mol Cell Neurosci 22(1):1-13PubMed: 12595234 MGI: J:82192
Fan L; Girnius S; Oakley B. 2004. Support of trigeminal sensory neurons by nonneuronal p75 neurotrophin receptors. Brain Res Dev Brain Res 150(1):23-39PubMed: 15126035 MGI: J:90280
Gschwendtner A; Liu Z; Hucho T; Bohatschek M; Kalla R; Dechant G; Raivich G. 2003. Regulation, cellular localization, and function of the p75 neurotrophin receptor (p75NTR) during the regeneration of facial motoneurons. Mol Cell Neurosci 24(2):307-22PubMed: 14572455 MGI: J:86223
Kim EY; Teh HS. 2004. Critical role of TNF receptor type-2 (p75) as a costimulator for IL-2 induction and T cell survival: a functional link to CD28. J Immunol 173(7):4500-9PubMed: 15383581 MGI: J:93724
Lee KF; Bachman K; Landis S; Jaenisch R. 1994. Dependence on p75 for innervation of some sympathetic targets. Science 263(5152):1447-9PubMed: 8128229 MGI: J:43749
Lee KF; Davies AM; Jaenisch R. 1994. p75-deficient embryonic dorsal root sensory and neonatal sympathetic neurons display a decreased sensitivity to NGF. Development 120(4):1027-33PubMed: 7600951 MGI: J:43751
Paul CE; Vereker E; Dickson KM; Barker PA. 2004. A pro-apoptotic fragment of the p75 neurotrophin receptor is expressed in p75NTRExonIV null mice. J Neurosci 24(8):1917-23PubMed: 14985432 MGI: J:90084
Sotthibundhu A; Sykes AM; Fox B; Underwood CK; Thangnipon W; Coulson EJ. 2008. Beta-amyloid(1-42) induces neuronal death through the p75 neurotrophin receptor. J Neurosci 28(15):3941-6PubMed: 18400893 MGI: J:132959

Additional - Ngfr^tm1Jae related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Ngfr
- Standard PCR:Ngfr
- Genotyping resources and troubleshooting
Breeding Considerations

This strain is a challenging breeder.

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.
- Additional Breeding and Husbandry Support
Appearance
- black
  Related Genotype: a/a
Citation
When using the p75^NGFR mouse strain in a publication, please cite the originating article(s) and include JAX stock #002213 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:p75NGFR

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Ngfrtm1Jae

Allele Symbol: Ngfrtm1Jae

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Ngfrtm1Jae related

Mammalian Phenotype Terms by Genotype

Genotype: Ngfrtm1Jae/Ngfrtm1JaeC;129S-Ngfr/J

cellular phenotype

nervous system phenotype

Genotype: Ngfrtm1Jae/Ngfrtm1Jaeinvolves: 129S1/Sv * 129S4/SvJae

nervous system phenotype

vision/eye phenotype

Genotype: Ngfrtm1Jae/Ngfrtm1Jaeinvolves: 129S4/SvJae * C57BL/6

nervous system phenotype

cellular phenotype

Genotype: Ngfrtm1Jae/Ngfrtm1Jaeinvolves: 129S4/SvJae * BALB/c

behavior/neurological phenotype

homeostasis/metabolism phenotype

integument phenotype

limbs/digits/tail phenotype

mammalian phenotype

muscle phenotype

nervous system phenotype

skeleton phenotype

craniofacial phenotype

growth/size/body region phenotype

Genotype: Ngfrtm1Jae/Ngfrtm1Jaeinvolves: 129S4/SvJae

behavior/neurological phenotype

nervous system phenotype

cellular phenotype

vision/eye phenotype

homeostasis/metabolism phenotype

immune system phenotype

Genotype: Ngfrtm1Jae/Ngfrtm1Jaeinvolves: 129 * BALB/c

cellular phenotype

nervous system phenotype

Genotype: Ngfrtm1Jae/Ngfrtm1Jaeinvolves: 129S4/SvJae * C57BL/6J

nervous system phenotype

Genotype: Ngfrtm1Jae/Ngfr+B6.129S4-Ngfr

cellular phenotype

respiratory system phenotype

nervous system phenotype

Genotype: Ngfrtm1Jae/Ngfrtm1JaeB6.129S4-Ngfr

craniofacial phenotype

digestive/alimentary phenotype

growth/size/body region phenotype

hematopoietic system phenotype

cardiovascular system phenotype

homeostasis/metabolism phenotype

immune system phenotype

liver/biliary system phenotype

nervous system phenotype

taste/olfaction phenotype

cellular phenotype

vision/eye phenotype

Genotype: Ngfrtm1Jae/Ngfrtm1JaeB6.129S4-Ngfr/J

cardiovascular system phenotype

homeostasis/metabolism phenotype

nervous system phenotype

hearing/vestibular/ear phenotype

References

Additional References

Additional - Ngfrtm1Jae related

Genotyping Protocols

Breeding Considerations

Appearance

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Also Known As:p75^NGFR

Ngfr^tm1Jae

Allele Symbol: Ngfr^tm1Jae

Genotype: Ngfr^tm1Jae related

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
C;129S-Ngfr/J

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
involves: 129S1/Sv * 129S4/SvJae

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
involves: 129S4/SvJae * C57BL/6

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
involves: 129S4/SvJae * BALB/c

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
involves: 129S4/SvJae

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
involves: 129 * BALB/c

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
involves: 129S4/SvJae * C57BL/6J

Genotype: Ngfr^tm1Jae/Ngfr⁺
B6.129S4-Ngfr

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
B6.129S4-Ngfr

Genotype: Ngfr^tm1Jae/Ngfr^tm1Jae
B6.129S4-Ngfr/J

Additional - Ngfr^tm1Jae related