Phenotypes associated with this allele

• Allele Symbol: Tnfrsf1a^tm1Imx
• Allele Name: targeted mutation 1, Immunex Research and Development Corporation
• Allele ID: MGI:1857468
• Summary: 21 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx	C57BL/6-Tnfrsf1a^tm1Imx	MGI:3689916
hm2	Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx	C57BL/6-Tnfrsf1a^tm1Imx/J	MGI:4461167
hm3	Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx	involves: 129S7/SvEvBrd * C57BL/6	MGI:2175019
hm4	Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx	involves: C57BL/6	MGI:5140855
ht5	Tnfrsf1a^tm1Imx/Tnfrsf1a^+	involves: C57BL/6	MGI:5573129
cn6	Xbp1^tm2Glm/Xbp1^tm2Glm Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx Tg(Vil1-cre)997Gum/0	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:5559521
cx7	Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx Il1r1^tm1Imx/Il1r1^tm1Imx	B6;129S-Tnfrsf1a^tm1Imx Il1r1^tm1Imx/J	MGI:3580519
cx8	Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx Tnfrsf1b^tm1Imx/Tnfrsf1b^tm1Imx	B6.129S-Tnfrsf1b^tm1Imx Tnfrsf1a^tm1Imx/J	MGI:6433775
cx9	Rela^tm1Bal/Rela^tm1Bal Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx	involves: 129S4/SvJae * C57BL/6	MGI:3799195
cx10	Ikbkg^tm1.1Dwat/Y Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NTac	MGI:5543236
cx11	Ikbkg^tm1.1Dwat/Ikbkg^tm1.1Dwat Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NTac	MGI:5543235
cx12	Lep^ob/Lep^ob Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx Tnfrsf1b^tm1Imx/Tnfrsf1b^tm1Imx	involves: 129S7/SvEvBrd * C57BL/6	MGI:2176437
cx13	Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx Tnfrsf1b^tm1Imx/Tnfrsf1b^tm1Imx	involves: 129S7/SvEvBrd * C57BL/6	MGI:3689914
cx14	Il1r1^tm1Imx/Il1r1^tm1Imx Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx	involves: 129S7/SvEvBrd * C57BL/6	MGI:3784419
cx15	Birc2^tm1.1Rbr/Birc2^tm1.1Rbr Birc3^tm1.1Rbr/Birc3^tm1.1Rbr Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx	involves: BALB/cJ * C57BL/6 * SJL	MGI:5319378
cx16	Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx Vasn^tm1Zgl/Vasn^tm1Zgl	involves: C57BL/6	MGI:5140854
cx17	Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx Tg(Thy1-APP)3Somm/0	involves: C57BL/6 * C57BL/6J * DBA/2	MGI:4833965
cx18	Ripk3^tm2Vmd/Ripk3^tm2Vmd Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx	involves: C57BL/6 * C57BL/6N	MGI:5614637
cx19	Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx Tg(Ins2-Cxcl13)1Cys/0	involves: C57BL/6 * DBA/2	MGI:3689370
cx20	Tnfaip3^tm1Ama/Tnfaip3^tm1Ama Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx	involves: C57BL/6J	MGI:3055284
cx21	Tnfaip3^tm1Ama/Tnfaip3^tm1Ama Tnfrsf1a^tm1Imx/Tnfrsf1a^+	involves: C57BL/6J	MGI:3055286

Genotype
MGI:3689916

hm1

• Allelic Composition: Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx
• Genetic Background: C57BL/6-Tnfrsf1a^tm1Imx

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

immune system

decreased microglial cell number ( J:112713 )

• numbers of microglial cells 23% lower than 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

decreased inflammatory response ( J:45147 )

• decreased pulmonary neutrophil accumulation in response to intranasal instillation of M. faeni 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)

lung inflammation ( J:120174 )

• lower levels of Il5, Il12, Il13, and Ifn-gamma in broncho-alveolar lavage fluid

• reduced numbers of T-alpha,beta cells in broncho-alveolar lavage fluid

increased susceptibility to bacterial infection ( J:45147 )

• 100% of mice succumb to a sublethal dose of Listeria monocytogenes 4 days post-infection

homeostasis/metabolism

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:78637 )

• 63% 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

hematopoietic system

decreased microglial cell number ( J:112713 )

• numbers of microglial cells 23% lower than controls after epileptic stimulation

liver/biliary system

abnormal oval cell physiology ( J:66448 )

• reduced oval cell response to a choline deficient diet and ethionine in the drinking water

neoplasm

increased skin papilloma incidence ( J:89088 )

• development after DMPA/TPA treatment is reduced

decreased tumor incidence ( J:66448 )

• lower incidence of tumors after 9 months on a choline deficient diet and ethionine in the drinking water

nervous system

decreased microglial cell number ( J:112713 )

• numbers of microglial cells 23% lower than controls after epileptic stimulation

abnormal nervous system physiology ( J:112713 )

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:78637 )

• 63% loss of striatal dopaminergic neurons in MPTP model of Parkinson's disease (controls lose 70%)

abnormal neuron proliferation ( J:112713 )

• 25% increase in the number of BrdU+ mature neurons in the dentate subgranular zone/granule cell layer

abnormal glutamate-mediated receptor currents ( J:152590 )

• increased glutamate currents

respiratory system

lung inflammation ( J:120174 )

• lower levels of Il5, Il12, Il13, and Ifn-gamma in broncho-alveolar lavage fluid

• reduced numbers of T-alpha,beta cells in broncho-alveolar lavage fluid

abnormal airway responsiveness ( J:120174 , J:143836 )

• fail to develop airway hyper responsiveness after "OVA" sensitization (J:120174)

abnormal respiratory mechanics ( J:143836 )

• peak inspiratory pressure is not affected by 2 hours of high stretch ventilation whereas controls experience rapid increases after 80-90 minutes

integument

increased skin papilloma incidence ( J:89088 )

• development after DMPA/TPA treatment is reduced

cellular

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:78637 )

• 63% loss of striatal dopaminergic neurons in MPTP model of Parkinson's disease (controls lose 70%)

abnormal neuron proliferation ( J:112713 )

• 25% increase in the number of BrdU+ mature neurons in the dentate subgranular zone/granule cell layer

Genotype
MGI:4461167

hm2

• Allelic Composition: Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx
• Genetic Background: C57BL/6-Tnfrsf1a^tm1Imx/J

mortality/aging

decreased susceptibility to induced morbidity/mortality ( J:160543 )

• mice treated with LPS and D-galactosamine fail to exhibit induced mortality unlike similarly treated wild-type mice

immune system

abnormal macrophage physiology ( J:160543 )

• TNF-stimulated peritoneal macrophages produce less IL6 and CXCL2 (MIP2) than similarly treated wild-type cells

decreased circulating interleukin-6 level ( J:160543 )

• following LPS challenge

increased circulating tumor necrosis factor level ( J:160543 )

• following LPS challenge

abnormal follicular dendritic cell morphology ( J:160543 )

• mice lack an intact follicular dendritic cell network and defined B- and T-cell zones unlike in wild-type mice

abnormal chemokine secretion ( J:160543 )

• TNF-stimulated peritoneal macrophages produce less CXCL2 (MIP2) than similarly treated wild-type cells

decreased interleukin-6 secretion ( J:160543 )

• TNF-stimulated peritoneal macrophages produce less IL6 than similarly treated wild-type cells

decreased susceptibility to endotoxin shock ( J:160543 )

• mice treated with LPS and D-galactosamine fail to exhibit induced mortality unlike similarly treated wild-type mice

homeostasis/metabolism

decreased circulating interleukin-6 level ( J:160543 )

• following LPS challenge

increased circulating tumor necrosis factor level ( J:160543 )

• following LPS challenge

hematopoietic system

abnormal macrophage physiology ( J:160543 )

• TNF-stimulated peritoneal macrophages produce less IL6 and CXCL2 (MIP2) than similarly treated wild-type cells

Genotype
MGI:2175019

hm3

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

immune system

abnormal immune system physiology ( J:45147 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
TNF receptor associated periodic syndrome		DOID:0090018	OMIM:142680	J:45147

Genotype
MGI:5140855

hm4

• Allelic Composition: Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx
• Genetic Background: involves: C57BL/6

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:210950 )

• all mice infected with Listeria monocytogenes die unlike wild-type mice

decreased susceptibility to induced morbidity/mortality ( J:210950 )

• no mice treated with TNF die unlike wild-type mice

immune system

impaired humoral immune response ( J:210950 )

• mice immunized with sheep red blood cells fail to exhibit germinal centers and follicular dendritic cell networks with no antibody response unlike wild-type mice

increased susceptibility to bacterial infection induced morbidity/mortality ( J:210950 )

• all mice infected with Listeria monocytogenes die unlike wild-type mice

cellular

increased sensitivity to induced cell death ( J:173568 )

• in mouse embryonic fibroblasts exposed to hypoxia

homeostasis/metabolism

abnormal response/metabolism to endogenous compounds ( J:210950 )

• TNF-treated mice fail to exhibit lethality, IL6 induction, hypothermia, sickness symptoms (ruffled fur, diarrhea and physical inactivity) or liver and kidney damage unlike wild-type mice

Genotype
MGI:5573129

ht5

• Allelic Composition: Tnfrsf1a^tm1Imx/Tnfrsf1a⁺
• Genetic Background: involves: C57BL/6

mortality/aging

decreased susceptibility to induced morbidity/mortality ( J:210950 )

• no mice treated with TNF die unlike all wild-type mice

immune system

decreased circulating interleukin-6 level ( J:210950 )

• decreased induction in TNF-treated mice

homeostasis/metabolism

decreased circulating interleukin-6 level ( J:210950 )

• decreased induction in TNF-treated mice

abnormal response/metabolism to endogenous compounds ( J:210950 )

• TNF-treated mice fail to exhibit lethality, as great IL6 induction, hypothermia, sickness symptoms (ruffled fur, diarrhea and physical inactivity) or liver and kidney damage unlike wild-type mice

Genotype
MGI:5559521

cn6

• Allelic Composition: Xbp1^tm2Glm/Xbp1^tm2Glm; Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx; Tg(Vil1-cre)997Gum/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * SJL

immune system

small intestinal inflammation ( J:206084 )

• enteritis is diminished compared to mice with IEC (intestinal epithelial cell) deletion of Xbp1 only

digestive/alimentary system

small intestinal inflammation ( J:206084 )

• enteritis is diminished compared to mice with IEC (intestinal epithelial cell) deletion of Xbp1 only

Genotype
MGI:3580519

cx7

• Allelic Composition: Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx; Il1r1^tm1Imx/Il1r1^tm1Imx
• Genetic Background: B6;129S-Tnfrsf1a^tm1Imx Il1r1^tm1Imx/J

behavior/neurological

abnormal sleep pattern ( J:137505 )

• during the last 6 hours of the dark period, mice exhibit increased awake time and less non-REM sleep compared with wild-type mice wild-type mice

• during the light period, mice exhibit fewer bouts of REM sleep compared with wild-type mice

• following sleep deprivation, mice fail to exhibit REM sleep rebound unlike wild-type mice and exhibit more time awake and less time in non-REM sleep during the first 6 hours of dark period compared with wild-type mice

• however, the length of REM sleep bouts is normal

homeostasis/metabolism

abnormal circadian temperature homeostasis ( J:137505 )

• brain temperature during the dark phase is higher than in wild-type mice

• mice exhibit lower brain temperature during the first 6 hours following sleep deprivation compared with wild-type mice

nervous system

abnormal brain wave pattern ( J:137505 )

• mice exhibit a greater contribution of slower frequencies to the total power of the non-REM sleep power spectra, measured by electrocorticogram, compared with wild-type mice

• theta power contributes less to total power compared to in wild-type mice

• following sleep deprivation, mice exhibit higher delta power compared with wild-type mice

Genotype
MGI:6433775

cx8

• 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:3799195

cx9

• Allelic Composition: Rela^tm1Bal/Rela^tm1Bal; Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx
• Genetic Background: involves: 129S4/SvJae * C57BL/6

mortality/aging

postnatal lethality, complete penetrance ( J:60742 )

• mice die between 6 and 17 days after birth

• however, prenatal lethality observed in Rela^tm1Bal homozygotes is reversed

hematopoietic system

abnormal thymus morphology ( J:60742 )

• at the time of death mice exhibit foci of degeneration in the thymus

extramedullary hematopoiesis ( J:60742 )

• in the liver of 2 to 7 day old mice

abnormal spleen germinal center morphology ( J:60742 )

• at the time of death, mice exhibit less compact germinal centers compared to in wild-type mice

decreased spleen white pulp amount ( J:60742 )

• at the time of death

liver/biliary system

liver inflammation ( J:60742 )

• at the time of death mice, exhibit acute hepatitis with massive neutrophilic infiltration and necrotic foci

focal hepatic necrosis ( J:60742 )

• at the time of death

cardiovascular system

heart inflammation ( J:60742 )

• at the time of death, some mice exhibit neutrophilic infiltration of the heart and lungs

growth/size/body

decreased body size ( J:60742 )

• within the first week after birth, mice become runted despite continued nursing

respiratory system

lung inflammation ( J:60742 )

• at the time of death, some mice exhibit neutrophilic infiltration of the heart and lungs

immune system

heart inflammation ( J:60742 )

• at the time of death, some mice exhibit neutrophilic infiltration of the heart and lungs

abnormal thymus morphology ( J:60742 )

• at the time of death mice exhibit foci of degeneration in the thymus

abnormal spleen germinal center morphology ( J:60742 )

• at the time of death, mice exhibit less compact germinal centers compared to in wild-type mice

decreased spleen white pulp amount ( J:60742 )

• at the time of death

liver inflammation ( J:60742 )

• at the time of death mice, exhibit acute hepatitis with massive neutrophilic infiltration and necrotic foci

lung inflammation ( J:60742 )

• at the time of death, some mice exhibit neutrophilic infiltration of the heart and lungs

endocrine/exocrine glands

abnormal thymus morphology ( J:60742 )

• at the time of death mice exhibit foci of degeneration in the thymus

Genotype
MGI:5543236

cx10

• Allelic Composition: Ikbkg^tm1.1Dwat/Y; Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NTac

mortality/aging

premature death ( J:202106 )

♂

preweaning lethality, incomplete penetrance ( J:202106 )

♂ • fewer than expected mice are generated

liver/biliary system

abnormal hepatocyte morphology ( J:202106 )

♂ • dysplasia with prominent nucleolar vacuoles

hepatic steatosis ( J:202106 )

♂ • macro- and microvesicular steatosis with centrilobular and zone 3 hepatitis

macrovesicular hepatic steatosis ( J:202106 )

microvesicular hepatic steatosis ( J:202106 )

liver fibrosis ( J:202106 )

♂ • moderate

abnormal liver physiology ( J:202106 )

♂ • liver disease

liver inflammation ( J:202106 )

♂ • in centrilobular and zone 3

abnormal liver regeneration ( J:202106 )

♂ • regenerative nodules

homeostasis/metabolism

increased circulating bilirubin level ( J:202106 )

♂

increased circulating alanine transaminase level ( J:202106 )

♂

increased circulating aspartate transaminase level ( J:202106 )

♂

increased circulating lactate dehydrogenase level ( J:202106 )

♂

immune system

immune system phenotype ( J:202106 )

♂N • mice do not exhibit skin lesions or spleen hypercellularity

liver inflammation ( J:202106 )

♂ • in centrilobular and zone 3

Genotype
MGI:5543235

cx11

• Allelic Composition: Ikbkg^tm1.1Dwat/Ikbkg^tm1.1Dwat; Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NTac

mortality/aging

premature death ( J:202106 )

♀

Genotype
MGI:2176437

cx12

• 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

cx13

• 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

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

Genotype
MGI:3784419

cx14

• Allelic Composition: Il1r1^tm1Imx/Il1r1^tm1Imx; Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

immune system

impaired neutrophil recruitment ( J:126652 )

• lungs infected with E. coli have decreased amounts of neutrophils that emigrate from the alveolar septae

• neutrophil numbers in circulation or sequestered within the alveolar septae are similar to wild-type

abnormal chemokine level ( J:126652 )

• there is 2-fold less levels of Cxcl1 (KC) found in the bronchoalveolar lavage fluid of lungs infected with E. coli compared to infected wild-type mice

decreased interleukin-6 secretion ( J:115094 )

• into the aqueous humor following induction of uveitis

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 and IL6 secretion into the aqueous humor compared with wild-type mice

osteomyelitis ( J:58851 )

• osteolytic lesions of molars are larger in these mice 2 weeks after bacterial inoculation of the dental pulp compared to either wild-type controls or to homozygotes that are null for just one gene

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

lung inflammation ( J:126652 )

• patchy pulmonary inflammation occurs spontaneously in about 2/3^rd of mice

• infiltrates contain mixed populations of leukocytes and are localized to the pleura, subpleura alveoli, and perivascular tissue

• eosinophilic crystalline deposits are found in the alveolar air spaces of inflamed areas

interstitial pneumonia ( J:126652 )

• lungs with pneumonia induced by E. coli inoculation have less neutrophil migration into the alveolar air spaces and less accumulation of extravascular plasma

increased susceptibility to bacterial infection ( J:58851 )

• mice have 4 log greater bacterial penetration of the dental pulp eight days after experimental bacterial infection

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 7 days after bacterial inoculation compared to control mice that still have intact dental pulp at 38 days post-innoculation

osteomyelitis ( J:58851 )

• osteolytic lesions of molars are larger in these mice 2 weeks after bacterial inoculation of the dental pulp compared to either wild-type controls or to homozygotes that are null for just one gene

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

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 5-fold higher than in wild-types 7 days after bacterial inoculation

respiratory system

lung inflammation ( J:126652 )

• patchy pulmonary inflammation occurs spontaneously in about 2/3^rd of mice

• infiltrates contain mixed populations of leukocytes and are localized to the pleura, subpleura alveoli, and perivascular tissue

• eosinophilic crystalline deposits are found in the alveolar air spaces of inflamed areas

interstitial pneumonia ( J:126652 )

• lungs with pneumonia induced by E. coli inoculation have less neutrophil migration into the alveolar air spaces and less accumulation of extravascular plasma

homeostasis/metabolism

abnormal chemokine level ( J:126652 )

• there is 2-fold less levels of Cxcl1 (KC) found in the bronchoalveolar lavage fluid of lungs infected with E. coli compared to infected wild-type mice

hematopoietic system

impaired neutrophil recruitment ( J:126652 )

• lungs infected with E. coli have decreased amounts of neutrophils that emigrate from the alveolar septae

• neutrophil numbers in circulation or sequestered within the alveolar septae are similar to wild-type

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 7 days after bacterial 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 7 days after bacterial inoculation compared to control mice that still have intact dental pulp at 38 days post-innoculation

Genotype
MGI:5319378

cx15

• Allelic Composition: Birc2^tm1.1Rbr/Birc2^tm1.1Rbr; Birc3^tm1.1Rbr/Birc3^tm1.1Rbr; Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx
• Genetic Background: involves: BALB/cJ * C57BL/6 * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:182515 )

• while mice are born alive none survive to weaning

Genotype
MGI:5140854

cx16

• Allelic Composition: Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx; Vasn^tm1Zgl/Vasn^tm1Zgl
• Genetic Background: involves: C57BL/6

reproductive system

reproductive system phenotype ( J:173568 )

N • male mice exhibit normal fertility and no abnormal male germ cell apoptosis

Genotype
MGI:4833965

cx17

• Allelic Composition: Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx; Tg(Thy1-APP)3Somm/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA/2

nervous system

nervous system phenotype ( J:134832 )

N • at 24 months, mice exhibit little neuronal loss unlike Tg(Thy1-APP)3Somm mice

microgliosis ( J:134832 )

• mice exhibit less microglial activation compared with Tg(Thy1-APP)3Somm mice

amyloid beta deposits ( J:134832 )

• at 24 months, mice exhibit reduced amyloid plaques compared with Tg(Thy1-APP)3Somm mice

cerebral amyloid angiopathy ( J:134832 )

• mice exhibit reduced cerebral amyloid angiopathy compared with Tg(Thy1-APP)3Somm mice

behavior/neurological

behavior/neurological phenotype ( J:134832 )

N • mice exhibit normal exploratory learning and memory retention unlike Tg(Thy1-APP)3Somm mice

hematopoietic system

microgliosis ( J:134832 )

• mice exhibit less microglial activation compared with Tg(Thy1-APP)3Somm mice

immune system

microgliosis ( J:134832 )

• mice exhibit less microglial activation compared with Tg(Thy1-APP)3Somm mice

homeostasis/metabolism

amyloid beta deposits ( J:134832 )

• at 24 months, mice exhibit reduced amyloid plaques compared with Tg(Thy1-APP)3Somm mice

cerebral amyloid angiopathy ( J:134832 )

• mice exhibit reduced cerebral amyloid angiopathy compared with Tg(Thy1-APP)3Somm mice

Genotype
MGI:5614637

cx18

• Allelic Composition: Ripk3^tm2Vmd/Ripk3^tm2Vmd; Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx
• Genetic Background: involves: C57BL/6 * C57BL/6N

mortality/aging

embryonic lethality prior to tooth bud stage ( J:209137 )

• embryos do not survive beyond around E11.5

Genotype
MGI:3689370

cx19

• Allelic Composition: Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx; Tg(Ins2-Cxcl13)1Cys/0
• Genetic Background: involves: C57BL/6 * DBA/2

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:110548 )

• frequency of pancreatic infiltrates is same as in wild-type transgenic littermates, but size of infiltrate is markedly reduced; no large infiltrates are detected and 50% fewer medium infiltrates are observed

• deficiency in accumulation of T cells and dendritic cells in infiltrates compared to wild-type transgenic mice is seen

immune system

abnormal lymph organ development ( J:110548 )

Genotype
MGI:3055284

cx20

• Allelic Composition: Tnfaip3^tm1Ama/Tnfaip3^tm1Ama; Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx
• Genetic Background: involves: C57BL/6J

mortality/aging

premature death ( J:92694 )

growth/size/body

decreased body size ( J:92694 )

cachexia ( J:92694 )

immune system

abnormal inflammatory response ( J:92694 )

• the absolute number and percentage of myeloid cells is increased in multiple tissues

Genotype
MGI:3055286

cx21

• Allelic Composition: Tnfaip3^tm1Ama/Tnfaip3^tm1Ama; Tnfrsf1a^tm1Imx/Tnfrsf1a⁺
• Genetic Background: involves: C57BL/6J

mortality/aging

premature death ( J:92694 )

growth/size/body

decreased body size ( J:92694 )

cachexia ( J:92694 )

immune system

abnormal inflammatory response ( J:92694 )

• the absolute number and percentage of myeloid cells is increased in multiple tissues