Phenotypes associated with this allele

• Allele Symbol: Tnfrsf1b^tm1Imx
• Allele Name: targeted mutation 1, Immunex Research and Development Corporation
• Allele ID: MGI:1860087
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tnfrsf1b^tm1Imx/Tnfrsf1b^tm1Imx	B6.129S7-Tnfrsf1b^tm1Imx	MGI:4830692
hm2	Tnfrsf1b^tm1Imx/Tnfrsf1b^tm1Imx	involves: 129S7/SvEvBrd * C57BL/6	MGI:2175020
cx3	Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx Tnfrsf1b^tm1Imx/Tnfrsf1b^tm1Imx	B6.129S-Tnfrsf1b^tm1Imx Tnfrsf1a^tm1Imx/J	MGI:6433775
cx4	Birc2^tm1.1Rbr/Birc2^tm1.1Rbr Birc3^tm1.1Rbr/Birc3^tm1.1Rbr Tnfrsf1b^tm1Imx/Tnfrsf1b^tm1Imx	involves: 129S7/SvEvBrd * BALB/cJ * C57BL/6 * SJL	MGI:5319379
cx5	Lep^ob/Lep^ob Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx Tnfrsf1b^tm1Imx/Tnfrsf1b^tm1Imx	involves: 129S7/SvEvBrd * C57BL/6	MGI:2176437
cx6	Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx Tnfrsf1b^tm1Imx/Tnfrsf1b^tm1Imx	involves: 129S7/SvEvBrd * C57BL/6	MGI:3689914

Genotype
MGI:4830692

hm1

• Allelic Composition: Tnfrsf1b^tm1Imx/Tnfrsf1b^tm1Imx
• Genetic Background: B6.129S7-Tnfrsf1b^tm1Imx

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

skeleton

skeleton phenotype ( J:135519 )

N • no increase in bone mineral density

respiratory system

respiratory system phenotype ( J:143836 )

N • display a rapid increase in peak inspiratory pressure when exposed to high stretch ventilation, as is seen in controls

abnormal lung compliance ( J:143836 )

homeostasis/metabolism

abnormal blood gas level ( J:143836 )

• decreased arterial pO2 after 2 hours of high stretch ventilation

• increased arterial pCO2 after 2 hours of high stretch ventilation

cardiovascular system

decreased systemic arterial blood pressure ( J:143836 )

• drops below 45mm Hg by 70 minutes of high stretch ventilation whereas controls require 90 minutes

Genotype
MGI:2175020

hm2

• Allelic Composition: Tnfrsf1b^tm1Imx/Tnfrsf1b^tm1Imx
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

immune system

microgliosis ( J:112713 )

• numbers of microglial cells significantly increased relative to controls after epileptic stimulation

increased circulating tumor necrosis factor level ( J:45147 )

• two hours post i.v. lipopolysaccharide (LPS) challenge serum levels are 5 fold higher than controls, however, TNF kinetics and activity are not altered

increased inflammatory response ( J:45147 )

• increased pulmonary neutrophil accumulation in response to intranasal instillation of M. faeni as compared to control, however monocyte and lymphocyte levels are comparable to control

lung inflammation ( J:120174 )

• increased numbers of T-gamma,delta cells in broncho-alveolar lavage fluid

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:59056 )

N • normal recovery after superficial injury causes an increased trans-epidermal water loss

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:78637 )

• 41% loss of striatal dopaminergic neurons in MPTP model of Parkinson's disease (controls lose 70%)

increased circulating tumor necrosis factor level ( J:45147 )

• two hours post i.v. lipopolysaccharide (LPS) challenge serum levels are 5 fold higher than controls, however, TNF kinetics and activity are not altered

nervous system

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:78637 )

• 41% loss of striatal dopaminergic neurons in MPTP model of Parkinson's disease (controls lose 70%)

microgliosis ( J:112713 )

• numbers of microglial cells significantly increased relative to controls after epileptic stimulation

abnormal glutamate-mediated receptor currents ( J:152590 )

• increased glutamate currents

neoplasm

increased skin papilloma incidence ( J:89088 )

• development after DMPA/TPA treatment is reduced

respiratory system

lung inflammation ( J:120174 )

• increased numbers of T-gamma,delta cells in broncho-alveolar lavage fluid

hematopoietic system

microgliosis ( J:112713 )

• numbers of microglial cells significantly increased relative to controls after epileptic stimulation

integument

increased skin papilloma incidence ( J:89088 )

• development after DMPA/TPA treatment is reduced

cellular

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:78637 )

• 41% loss of striatal dopaminergic neurons in MPTP model of Parkinson's disease (controls lose 70%)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	essential hypertension	DOID:10825	OMIM:145500 OMIM:603918 OMIM:604329 OMIM:607329 OMIM:608742 OMIM:610261 OMIM:610262 OMIM:610948 OMIM:611014	J:45147
NOT	familial combined hyperlipidemia	DOID:13809	OMIM:144250	J:45147

Genotype
MGI:6433775

cx3

• Allelic Composition: Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx; Tnfrsf1b^tm1Imx/Tnfrsf1b^tm1Imx
• Genetic Background: B6.129S-Tnfrsf1b^tm1Imx Tnfrsf1a^tm1Imx/J

immune system

decreased susceptibility to Coronaviridae infection ( J:288523 )

• mice infected with mouse-adapted SARS-CoV MA15 exhibit protection from weight loss that is seen in wild-type mice and decreased viral titers

Genotype
MGI:5319379

cx4

• Allelic Composition: Birc2^tm1.1Rbr/Birc2^tm1.1Rbr; Birc3^tm1.1Rbr/Birc3^tm1.1Rbr; Tnfrsf1b^tm1Imx/Tnfrsf1b^tm1Imx
• Genetic Background: involves: 129S7/SvEvBrd * BALB/cJ * C57BL/6 * SJL

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:182515 )

• around E10.5

Genotype
MGI:2176437

cx5

• Allelic Composition: Lep^ob/Lep^ob; Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx; Tnfrsf1b^tm1Imx/Tnfrsf1b^tm1Imx
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

homeostasis/metabolism

decreased circulating insulin level ( J:55722 )

• plasma insulin levels are reduced significantly compared to homozygous Lep mutants

abnormal metabolism ( J:55722 )

• 52% reduction in plasminogen activator inhibitor (PAI-1) antigen in the plasma

• 78% reduction in PAI-1 mRNA expression and 80% reduction in TGF-beta gene expression in adipose tissue

adipose tissue

abnormal adipose tissue morphology ( J:55722 )

• 78% reduction in PAI-1 mRNA expression and 80% reduction in TGF-beta gene expression in adipose tissue

Genotype
MGI:3689914

cx6

• Allelic Composition: Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx; Tnfrsf1b^tm1Imx/Tnfrsf1b^tm1Imx
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

mortality/aging

decreased susceptibility to induced morbidity/mortality ( J:48865 )

• enhanced survival after caecal ligation and puncture

immune system

decreased microglial cell activation ( J:33864 )

• reduced microglial response to excitotoxic injury

increased circulating tumor necrosis factor level ( J:45147 )

• two hours post lipopolysaccharide (LPS) challenge serum levels are 15-20 fold higher than controls, however, TNF kinetics and activity are not altered

decreased susceptibility to experimental autoimmune uveoretinitis ( J:115094 )

• following reverse passive Arthus reaction to induce uveitis, mice exhibit reduced cellular infiltration into the anterior and posterior segments compared with wild-type mice

decreased susceptibility to induced arthritis ( J:120707 )

• do not respond to collagen type II injections as do controls by developing arthritis for at least 14 days

decreased inflammatory response ( J:45147 )

• M. faeni- induced neutrophil accumulation in the lung is decreased as compared to control, however monocyte and lymphocyte levels are comparable to control

decreased susceptibility to endotoxin shock ( J:45147 )

• exhibits resistance to a lethal LPS dose plus hepatoxin D-gal (increases sensitivity to LPS)

osteomyelitis ( J:58851 )

• osteolytic lesions of molars are significantly larger in these mice 2 weeks after bacterial inoculation of the dental pulp

• the osteolytic lesions continue to be larger for at least 38 days after innoculation

increased susceptibility to bacterial infection ( J:58851 )

• mice have 3 log greater bacterial penetration of the dental pulp eight days after experimental bacterial infection

homeostasis/metabolism

increased myocardial infarct size ( J:62223 )

• 40% larger infarction than controls after coronary artery occlusion

• extent of necrosis in ventricles is similar to controls

• apoptosis peaks earlier and higher than for controls

increased susceptibility to neuronal excitotoxicity ( J:33864 )

• increased susceptibility to kainic acid damage

• 30-50% neuron loss at kainic acid doses causing only minimal hippocampal damage in controls

• susceptibility to kainic acid damage is not reduced by TNF treatment

increased circulating tumor necrosis factor level ( J:45147 )

• two hours post lipopolysaccharide (LPS) challenge serum levels are 15-20 fold higher than controls, however, TNF kinetics and activity are not altered

abnormal thrombosis ( J:117987 )

• TNF alpha induced thrombus formation is delayed

abnormal body temperature homeostasis ( J:48865 )

• hypothermic response to caecal ligation and puncture much shorter in duration than for controls

• febrile response to caecal ligation and puncture earlier in onset in males

decreased physiological sensitivity to xenobiotic ( J:51349 )

• fail to develop fibroproliferative lesions at bronchiolar-alveolar duct junctions when exposed to chrysotile asbestos fibers

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:78637 )

• protected against loss of striatal dopaminergic neurons in MPTP model of Parkinson's disease (controls lose 70%)

• also protected against tyrosin hydroxylase loss

• no loss of tyrosine hydroxylase immunoreactive nerve terminals

increased cerebral infarct size ( J:33864 )

• significantly increased area of infarct after middle cerebral artery occlusion

abnormal bone healing ( J:70467 )

• enlarged calluses formed on long bone fractures during healing at days 14, 21, and 28

• bones are fragile and prone to re-breaking

• delayed removal of calcified cartillage

• delayed mesenchymal cell differentiation

cellular

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:78637 )

• protected against loss of striatal dopaminergic neurons in MPTP model of Parkinson's disease (controls lose 70%)

• also protected against tyrosin hydroxylase loss

• no loss of tyrosine hydroxylase immunoreactive nerve terminals

increased susceptibility to neuronal excitotoxicity ( J:33864 )

• increased susceptibility to kainic acid damage

• 30-50% neuron loss at kainic acid doses causing only minimal hippocampal damage in controls

• susceptibility to kainic acid damage is not reduced by TNF treatment

dental pulp necrosis ( J:58851 )

• mice have significantly higher necrosis scores of the dental pulp seven days after bacterial inoculation

• complete necrosis of the dental pulp is observed by 21 days after inoculation compared to control mice that still have intact dental pulp at 38 days post-innoculation

skeleton

dental pulp necrosis ( J:58851 )

• mice have significantly higher necrosis scores of the dental pulp seven days after bacterial inoculation

• complete necrosis of the dental pulp is observed by 21 days after inoculation compared to control mice that still have intact dental pulp at 38 days post-innoculation

abnormal bone healing ( J:70467 )

• enlarged calluses formed on long bone fractures during healing at days 14, 21, and 28

• bones are fragile and prone to re-breaking

• delayed removal of calcified cartillage

• delayed mesenchymal cell differentiation

decreased susceptibility to induced arthritis ( J:120707 )

• do not respond to collagen type II injections as do controls by developing arthritis for at least 14 days

osteomyelitis ( J:58851 )

• osteolytic lesions of molars are significantly larger in these mice 2 weeks after bacterial inoculation of the dental pulp

• the osteolytic lesions continue to be larger for at least 38 days after innoculation

abnormal trabecular bone morphology ( J:70467 )

• no induction of intramembranous bone on periosteal surfaces after 21 days of healing

• lack of trabecular bridging

• delayed formation of new trabecular bone after bone marrow cannulation

• extensive necrotic tissue and hematomas remain 3 days after bone marrow cannulation

increased bone resorption ( J:58851 )

• there is significantly more osteoclastogenesis that occurs in molars between 7 and 21 days after bacterial infection of the dental pulp

• osteoclast activity of the molars is almost 2-fold higher than in wild-types 7 days after bacterial inoculation

nervous system

nervous system phenotype ( J:33864 )

N • no overt phenotype when unstressed

seizures ( J:112713 )

• 44% higher level of generalized convulsions in the 2 hours following 1 hour of electrical stimulation in the hippocampus

increased cerebral infarct size ( J:33864 )

• significantly increased area of infarct after middle cerebral artery occlusion

abnormal nervous system morphology ( J:78637 )

abnormal glial cell physiology ( J:78637 )

• glial response to neuronal injury is blunted

decreased microglial cell activation ( J:33864 )

• reduced microglial response to excitotoxic injury

abnormal neuron physiology ( J:33864 )

• long term neuron survival in culture is reduced

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:78637 )

• protected against loss of striatal dopaminergic neurons in MPTP model of Parkinson's disease (controls lose 70%)

• also protected against tyrosin hydroxylase loss

• no loss of tyrosine hydroxylase immunoreactive nerve terminals

increased susceptibility to neuronal excitotoxicity ( J:33864 )

• increased susceptibility to kainic acid damage

• 30-50% neuron loss at kainic acid doses causing only minimal hippocampal damage in controls

• susceptibility to kainic acid damage is not reduced by TNF treatment

behavior/neurological

decreased food intake ( J:48865 )

• reduced food intake at 24 hours but not at 48 hours after caecal ligation and puncture in males

seizures ( J:112713 )

• 44% higher level of generalized convulsions in the 2 hours following 1 hour of electrical stimulation in the hippocampus

respiratory system

pulmonary fibrosis ( J:51349 )

• fail to develop fibroproliferative lesions at bronchiolar-alveolar duct junctions when exposed to chrysotile asbestos fibers

cardiovascular system

abnormal retina blood vessel morphology ( J:104652 )

• more extensive avascular region develops on the retina 17 days after treatment of mice with 75% oxygen for 5 days

• recovery of deep retinal vessels delayed relative to controls

• rate of neovascularization higher at 21 days after treatment than in controls

increased myocardial infarct size ( J:62223 )

• 40% larger infarction than controls after coronary artery occlusion

• extent of necrosis in ventricles is similar to controls

• apoptosis peaks earlier and higher than for controls

renal/urinary system

abnormal kidney morphology ( J:69294 )

• reduced interstitial volume

renal interstitial fibrosis ( J:69294 )

• more modest development of progressive interstitial fibrosis after uretera; ligation than in controls

• collagen IV deposition

• improved by enalapril treatment

muscle

impaired skeletal muscle regeneration ( J:104990 )

• recovery after cardiotoxin damage to the soleus muscle is slowed

• few well defined myofibers 5 days after treatment when the control animal is almost normal

• severe inflammatory infiltration persists through 5 days

• extensive calcium deposits at 5 days

• cross-sectional area of myofibers at 68.7% of pretreatment condition at 12 days after treatment

• contractile force recovery is 53.9% of preatreatment level compared to 75.8% for controls

vision/eye

abnormal retina blood vessel morphology ( J:104652 )

• more extensive avascular region develops on the retina 17 days after treatment of mice with 75% oxygen for 5 days

• recovery of deep retinal vessels delayed relative to controls

• rate of neovascularization higher at 21 days after treatment than in controls

hematopoietic system

decreased microglial cell activation ( J:33864 )

• reduced microglial response to excitotoxic injury

craniofacial

dental pulp necrosis ( J:58851 )

• mice have significantly higher necrosis scores of the dental pulp seven days after bacterial inoculation

• complete necrosis of the dental pulp is observed by 21 days after inoculation compared to control mice that still have intact dental pulp at 38 days post-innoculation

growth/size/body

dental pulp necrosis ( J:58851 )

• mice have significantly higher necrosis scores of the dental pulp seven days after bacterial inoculation

• complete necrosis of the dental pulp is observed by 21 days after inoculation compared to control mice that still have intact dental pulp at 38 days post-innoculation