JAX
Mouse Strain Datasheet - 002124
C;129S-Ngfrtm1Jae/J
Also Known As: p75NGFR
Mice homozygous for the Ngfrtm1Jae mutation display a decreased cutaneous innervation by calcitonin gene-related peptide- and substance P-immunoreactive sensory fibers. Pineal glands lack sympathetic innervation, and innervation to sweat glands on foot pads is either reduced or absent. p75-deficient dorsal root ganglion and superior cervical ganglion neurons show a 2- to 3-fold decrease in sensitivity to nerve growth factor at embryonic day 15 and postnatal day 3, respectively.
Donating Investigator
Dr. Rudolf Jaenisch, Whitehead Institute (MIT)
Genetic overview
| Genetic Background | Generation |
|---|---|
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Ngfrtm1Jae
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Targeted (Null/Knockout) | Ngfr | nerve growth factor receptor (TNFR superfamily, member 16) |
Research Applications
- Sensorineural Research
- Apoptosis Research
- Neurobiology Research
Detailed Description
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 4 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 2- to 3-fold decreased sensitivity to NGF at embryonic day 15 and postnatal day 3, respectively. These ages coincide with the peak of naturally occurring cell death.
Development
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.
Control Suggestions
- There are no appropriate physiological controls for this mutant strain. However, if you must have a control you may use either 129S3/SvImJ (Stock No. 002448) or BALB/cJ mice (Stock No. 000651) These strains also serve as DNA controls.
Approximate Controls
Additional Information
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):737-49. PubMed: 1317267MGI: J:43748
Ngfrtm1Jae
Allele Symbol: Ngfrtm1Jae
| Allele Name | targeted mutation 1, Rudolf Jaenisch |
|---|---|
| Allele Type | Targeted (Null/Knockout) |
| Allele Synonym(s) | NGFRtm1Jac; Ngfr-; p75(III)-; p75-; p75-KO; p75NGFR; p75NTR-; p75NTR KO; p75NTRexon3-null; p75exonIII-; p75NTR-; p75NTR/ExonIII-; p75e3- |
| Gene Symbol and Name | Ngfr, nerve growth factor receptor (TNFR superfamily, member 16) |
| Gene Synonym(s) | CD271; Gp80-LNGFR; LNGFR; RNNGFRR; TNFRSF16; Tnfrsf16; p75; p75 neurotrophin receptor; p75(NTR); p75NGFR; p75NTR |
| 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 | Dr. Rudolf Jaenisch, Whitehead Institute (MIT) |
Disease Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
- Sensorineural Research
- Nociception
Genotype: Ngfrtm1Jae related
- Apoptosis Research
- Death Receptors
- Neurobiology Research
- Neurotrophic Factor Defects
- Receptor Defects
Mammalian Phenotype Terms by Genotype
Genotype: Ngfrtm1Jae/Ngfrtm1Jae
involves: 129 * BALB/c
nervous system phenotype
- abnormal axon extension
- 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 (MGI Ref ID J:96121)
- 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 (MGI Ref ID J:96121)
cellular phenotype
- abnormal axon extension
- 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 (MGI Ref ID J:96121)
- 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 (MGI Ref ID J:96121)
Genotype: Ngfrtm1Jae/Ngfrtm1Jae
involves: 129S4/SvJae * BALB/c
nervous system phenotype
- abnormal dorsal root ganglion morphology
- mice exhibit a loss of myelinated fibers in the dorsal root ganglion (MGI Ref ID J:53825)
- abnormal proprioceptive neuron morphology
- mice exhibit a 50% loss of proprioreceptive neurons in L4 of the dorsal root ganglion (MGI Ref ID J:53825)
- abnormal sensory neuron innervation pattern
- at 3 to 5 months, Pde6a+ pulpal neurons are decreased (MGI Ref ID J:42087)
- however, sympathetic innervation of the iris and salivary glands is normal (MGI Ref ID J:43748)
- only a few single fibers are present in the subepidermis and none are detected in the epidermis of fore- and hindlimb paws (MGI Ref ID J:43748)
- reduced innervation is not restricted to hairless patches (MGI Ref ID J:43748)
- the dermis of fore- and hindlimb paws either lacks or have reduced numbers of Pde6a+ sensory fibers and small-diameter nerves are absent (MGI Ref ID J:43748)
- 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 (MGI Ref ID J:53825)
- 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 (MGI Ref ID J:53825)
growth/size/body region phenotype
- abnormal molar crown morphology
- abnormal molar morphology
- mandibular molar occlusal facets are longer than in wild-type mice (MGI Ref ID J:42087)
- abnormal mouth morphology
- the height of the oral cavity is reduced (MGI Ref ID J:42087)
- abnormal tooth morphology
- increased signs of wear on molars (MGI Ref ID J:42087)
skeleton phenotype
- abnormal molar crown morphology
- abnormal molar morphology
- mandibular molar occlusal facets are longer than in wild-type mice (MGI Ref ID J:42087)
- abnormal tooth morphology
- increased signs of wear on molars (MGI Ref ID J:42087)
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) (MGI Ref ID J:53825)
- 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 (MGI Ref ID J:53825)
behavior/neurological phenotype
- abnormal sensory capabilities/reflexes/nociception
- prolonged latency in hot plate test (MGI Ref ID J:43748)
homeostasis/metabolism phenotype
- extremity edema
- at 4 months of age, mice exbihit edema in the fore- and hindlimb paws (MGI Ref ID J:43748)
limbs/digits/tail phenotype
- ulcerated paws
- at 4 months of age, fore- and hindlimb paws become edematous and develop severe ulcers (MGI Ref ID J:43748)
- epidermis and epidermal structures are lost from areas affected by ulcers (MGI Ref ID J:43748)
- excessive epidermal proliferation is present at the edges of ulcers (MGI Ref ID J:43748)
- ulcers are complicated by secondary infections that result in the lose of toenails and hair (MGI Ref ID J:43748)
- ulcers progress more proximally (MGI Ref ID J:43748)
renal/urinary system phenotype
- renal/urinary system phenotype
- unlike in studies using p75NGFR oligonucleotide knockdown, kidney function is normal (MGI Ref ID J:43748)
craniofacial phenotype
- abnormal molar crown morphology
- abnormal molar morphology
- mandibular molar occlusal facets are longer than in wild-type mice (MGI Ref ID J:42087)
- abnormal mouth morphology
- the height of the oral cavity is reduced (MGI Ref ID J:42087)
- abnormal tooth morphology
- increased signs of wear on molars (MGI Ref ID J:42087)
integument phenotype
- absent hair follicles
- loss of follicles, at distal extremities, progressive to more proximal regions (MGI Ref ID J:43748)
The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain
Genotype: Ngfrtm1Jae/Ngfr+
B6.129S4-Ngfrtm1Jae
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 Ngfrtm1Jae homozygotes (MGI Ref ID J:127639)
- abnormal neuron differentiation
- nerve coverage is less than in wild-type mice but not as severely reduced as in Ngfrtm1Jae homozygotes (MGI Ref ID J:127639)
respiratory system phenotype
- decreased airway responsiveness
- however, interferon-gamma production following exposure to provocation agent is normal (MGI Ref ID J:115419)
- total leukocytes, eosinophils and lymphocytes do not increase as in wild-type following exposure to provocation agent (MGI Ref ID J:115419)
- unlike in exposed wild-type mice IL-4 and IL-5 production is not increased (MGI Ref ID J:115419)
- unlike in exposed wild-type mice, no pulmonary eosinophilic inflammation is observed (MGI Ref ID J:115419)
- 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) for wild-type mice) (MGI Ref ID J:115419)
- while IgE levels increase following exposure to provocation they do not increase as much as in wild-type mice (MGI Ref ID J:115419)
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 Ngfrtm1Jae homozygotes (MGI Ref ID J:127639)
- abnormal neuron differentiation
- nerve coverage is less than in wild-type mice but not as severely reduced as in Ngfrtm1Jae homozygotes (MGI Ref ID J:127639)
Genotype: Ngfrtm1Jae/Ngfrtm1Jae
involves: 129S4/SvJae * C57BL/6
nervous system phenotype
- 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 (MGI Ref ID J:139381)
- this lack of growth disadvantage in non-stimulated axons is due to less axon degeneration than occurs to wild-type neurons (MGI Ref ID J:139381)
- 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 (MGI Ref ID J:139381)
- 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 (MGI Ref ID J:139381)
- mutant mice have a similar percentage of SCG neurons that connect to both eyes at P20 but this percentage does not decrease with age (MGI Ref ID J:139381)
- sympathetic neurons of the superior cervical ganglion (SCG) have improper pruning of axons from neurons that reach into both eye compartments (MGI Ref ID J:139381)
cellular phenotype
- 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 (MGI Ref ID J:139381)
- this lack of growth disadvantage in non-stimulated axons is due to less axon degeneration than occurs to wild-type neurons (MGI Ref ID J:139381)
- 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 (MGI Ref ID J:139381)
- 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 (MGI Ref ID J:139381)
- mutant mice have a similar percentage of SCG neurons that connect to both eyes at P20 but this percentage does not decrease with age (MGI Ref ID J:139381)
- sympathetic neurons of the superior cervical ganglion (SCG) have improper pruning of axons from neurons that reach into both eye compartments (MGI Ref ID J:139381)
Genotype: Ngfrtm1Jae/Ngfrtm1Jae
B6.129S4-Ngfrtm1Jae
nervous system phenotype
- abnormal axon extension
- growth cones from dorsal root ganglion neurons are more sensitive to Sema3A repulsion than wild-type neurons (MGI Ref ID J:127639)
- however, increased sensitivity to Sema3A repulsion is alleviated in a double heterozygote cross of Ngfr and Sema3A (MGI Ref ID J:127639)
- 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) (MGI Ref ID J:127639)
- abnormal innervation pattern to muscle
- abnormal neuron differentiation
- peripheral nerves in the hindlimb, forelimb, and trigeminal ganglia are severely stunted compared to in wild-type mice (MGI Ref ID J:127639)
- abnormal neuron morphology
- at 60 weeks sympathetic neuron cell bodies are 25% smaller than in wild-type mice (MGI Ref ID J:128451)
- like wild-type neurons, cultured superior cervical ganglion neurons are resistant to apoptosis induced by pro-NGF and pro-BDNF (MGI Ref ID J:128451)
- the number of sympathetic neurons is increased 33% at P4 and 39% at P15 compared to in wild-type mice (MGI Ref ID J:128451)
- unlike in wild-type mice, superior cervical ganglion are protected from age-related apoptosis (MGI Ref ID J:128451)
- 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 (MGI Ref ID J:90280)
- innervation of the fungiform papillae are reduced (MGI Ref ID J:90280)
- innervation of the somatosensory prominences is reduced (MGI Ref ID J:90280)
- increased neuron number
- the number of sympathetic neurons is increased 33% at P4 and 39% at P15 compared to in wild-type mice (MGI Ref ID J:128451)
- 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 (MGI Ref ID J:115542)
- 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 (MGI Ref ID J:115542)
craniofacial phenotype
- abnormal circumvallate papillae morphology
- 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 (MGI Ref ID J:90280)
cellular phenotype
- abnormal axon extension
- growth cones from dorsal root ganglion neurons are more sensitive to Sema3A repulsion than wild-type neurons (MGI Ref ID J:127639)
- however, increased sensitivity to Sema3A repulsion is alleviated in a double heterozygote cross of Ngfr and Sema3A (MGI Ref ID J:127639)
- 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) (MGI Ref ID J:127639)
- abnormal neuron differentiation
- peripheral nerves in the hindlimb, forelimb, and trigeminal ganglia are severely stunted compared to in wild-type mice (MGI Ref ID J:127639)
growth/size/body region phenotype
- abnormal circumvallate papillae morphology
- 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 (MGI Ref ID J:90280)
digestive/alimentary phenotype
- abnormal circumvallate papillae morphology
- 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 (MGI Ref ID J:90280)
cardiovascular 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 (MGI Ref ID J:120368)
- abnormal vascular wound healing
- apoptosis in neointimal lesions is decreased by 60% to 70% (MGI Ref ID J:109753)
- 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 (MGI Ref ID J:109753)
- however, infiltration of inflammatory cells is normal (MGI Ref ID J:109753)
taste/olfaction phenotype
- abnormal gustatory papillae taste bud morphology
immune 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 (MGI Ref ID J:120368)
- increased susceptibility to experimental autoimmune encephalomyelitis
- mice display considerable infiltration of fibronectin into the spinal cord parenchyma (MGI Ref ID J:112769)
- B220+ B cells make up 6% of cells in the inflammatory cuffs compared to 15% in wild-type mice immunized with MOG35-55 (MGI Ref ID J:112769)
- however, the number of double-positive (monocyte) cells is normal (MGI Ref ID J:112769)
- mice have an increased risk of developing severe experimental autoimmune encephalomyelitis compared to wild-type mice (MGI Ref ID J:112769)
- 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 (MGI Ref ID J:112769)
- polymorphonuclear cells are reduced by half compared to in wild-type mice immunized with MOG35-55 (MGI Ref ID J:112769)
- the population of Iba-1+ cells in the inflammatory cuffs is reduced by 10% compared to in wild-type mice immunized with MOG35-55 (MGI Ref ID J:112769)
homeostasis/metabolism phenotype
- abnormal vascular wound healing
- apoptosis in neointimal lesions is decreased by 60% to 70% (MGI Ref ID J:109753)
- 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 (MGI Ref ID J:109753)
- however, infiltration of inflammatory cells is normal (MGI Ref ID J:109753)
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 (MGI Ref ID J:120368)
vision/eye phenotype
- 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 (MGI Ref ID J:115542)
- 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 (MGI Ref ID J:115542)
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 (MGI Ref ID J:120368)
Genotype: Ngfrtm1Jae/Ngfrtm1Jae
involves: 129S4/SvJae
nervous system phenotype
- abnormal axon guidance
- abnormal cholinergic neuron morphology
- increased size of cholinergic forebrain neurons (MGI Ref ID J:62379)
- abnormal retinal ganglion cell morphology
- 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 (MGI Ref ID J:145459)
- at P8, the termination zone of retinal ganglion cell axons in the superior colliculus is shifted anteriorly compared to in wild-type mice (MGI Ref ID J:145459)
- 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 (MGI Ref ID J:145459)
- abnormal sensory neuron innervation pattern
- absence of sensory innervation to pineal and sweat glands (MGI Ref ID J:43749)
- 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 (MGI Ref ID J:145459)
- however, total area of the superior colliculus is normal (MGI Ref ID J:145459)
- 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 (MGI Ref ID J:145459)
- abnormal trigeminal ganglion morphology
- ophthalmic branch of the trigeminal ganglion is severely truncated at E12.5 (MGI Ref ID J:157604)
- decreased neuron apoptosis
behavior/neurological phenotype
- abnormal spatial learning
- spatial learning is improved compared to in wild-type mice without deterioration with age (MGI Ref ID J:62379)
vision/eye phenotype
- abnormal eye physiology
- mice subjected to intraocular injection of the pro form of nerve growth factor are protected from induced retinal ganglion cell death (MGI Ref ID J:157549)
- abnormal retinal ganglion cell morphology
- 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 (MGI Ref ID J:145459)
- at P8, the termination zone of retinal ganglion cell axons in the superior colliculus is shifted anteriorly compared to in wild-type mice (MGI Ref ID J:145459)
- 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 (MGI Ref ID J:145459)
homeostasis/metabolism phenotype
- abnormal tumor necrosis factor level
- the pro form of nerve growth factor fails to induce TNF expression in retinas (MGI Ref ID J:157549)
immune system phenotype
- abnormal tumor necrosis factor level
- the pro form of nerve growth factor fails to induce TNF expression in retinas (MGI Ref ID J:157549)
cellular phenotype
- abnormal axon guidance
Genotype: Ngfrtm1Jae/Ngfrtm1Jae
C;129S-Ngfrtm1Jae/J
nervous system phenotype
- abnormal neuron apoptosis
- reduced levels of neuronal cell death (MGI Ref ID J:46125)
cellular phenotype
- abnormal neuron apoptosis
- reduced levels of neuronal cell death (MGI Ref ID J:46125)
Genotype: Ngfrtm1Jae/Ngfrtm1Jae
involves: 129S4/SvJae * C57BL/6J
nervous system phenotype
- abnormal peripheral nervous system regeneration
- motor axonal regeneration is increased in the tibial nerve cross-suture (MGI Ref ID J:116954)
- decreased motor neuron number
- the number of motor neurons in tibial nerve is reduced (MGI Ref ID J:116954)
Genotype: Ngfrtm1Jae/Ngfrtm1Jae
involves: 129S1/Sv * 129S4/SvJae
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 (MGI Ref ID J:145459)
- 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 (MGI Ref ID J:145459)
- 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 (MGI Ref ID J:145459)
- 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 (MGI Ref ID J:145459)
vision/eye 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 (MGI Ref ID J:145459)
- 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 (MGI Ref ID J:145459)
Genotype: Ngfrtm1Jae/Ngfrtm1Jae
B6.129S4-Ngfrtm1Jae/J
hearing/vestibular/ear phenotype
- cochlear hair cell degeneration
- by 6 months, male homozygotes exhibit absence or damage of cochlear HCs in both the basal and upper turns (MGI Ref ID J:110434)
- however, IHCs are still present and morphologically normal at 4 months, suggesting that SGN's dendrites connecting the IHCs are damaged earlier than IHCs (MGI Ref ID J:110434)
- increased or absent threshold for auditory brainstem response
- at 4 months of age, male homozygotes exhibit a significant elevation (>33 dB SPL) in click-evoked ABR thresholds relative to wild-type males (MGI Ref ID J:110434)
- 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) (MGI Ref ID J:110434)
- however, no significant differences in click-evoked ABR thresholds are observed at 1 month, consistent with a normal cochlear structure at this age (MGI Ref ID J:110434)
- increased susceptibility to age-related hearing loss
- organ of Corti degeneration
- 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 (MGI Ref ID J:110434)
nervous system phenotype
- cochlear ganglion degeneration
- 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 (MGI Ref ID J:110434)
- 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 (MGI Ref ID J:110434)
- starting at 1 month, male homozygotes show a slight (15.7%) but progressive loss of SGNs from the basal to the apical cochlear turns (MGI Ref ID J:110434)
- cochlear hair cell degeneration
- by 6 months, male homozygotes exhibit absence or damage of cochlear HCs in both the basal and upper turns (MGI Ref ID J:110434)
- however, IHCs are still present and morphologically normal at 4 months, suggesting that SGN's dendrites connecting the IHCs are damaged earlier than IHCs (MGI Ref ID J:110434)
cardiovascular system phenotype
- decreased myocardial infarction size
- 10 days after myocardial ischemic/reperfusion injury (MGI Ref ID J:190893)
homeostasis/metabolism phenotype
- decreased myocardial infarction size
- 10 days after myocardial ischemic/reperfusion injury (MGI Ref ID J:190893)
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):737-49. PubMed: 1317267MGI: J:43748
Additional References
- Lee KF; Bachman K; Landis S; Jaenisch R. 1994. Dependence on p75 for innervation of some sympathetic targets. Science 263(5152):1447-9. PubMed: 8128229MGI: 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):1027-33. PubMed: 7600951MGI: J:43751
- McQuillen PS; DeFreitas MF; Zada G; Shatz CJ. 2002. A novel role for p75NTR in subplate growth cone complexity and visual thalamocortical innervation. J Neurosci 22(9):3580-93. PubMed: 11978834MGI: J:76254
- Ward NL; Stanford LE; Brown RE; Hagg T. 2000. Cholinergic medial septum neurons do not degenerate in aged 129/Sv control or p75(NGFR)-/-mice(*) Neurobiol Aging 21(1):125-34. PubMed: 10794857MGI: J:62452
Additional - Ngfrtm1Jae related
- Agerman K; Baudet C; Fundin B; Willson C; Ernfors P. 2000. Attenuation of a caspase-3 dependent cell death in NT4- and p75-deficient embryonic sensory neurons. Mol Cell Neurosci 16(3):258-68. PubMed: 10995552MGI: J:123022
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