Mouse Genome Informatics
hm1
    Tnfrsf1btm1Imx/Tnfrsf1btm1Imx
B6.129S7-Tnfrsf1btm1Imx
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
N
• no increase in bone mineral density (J:135519)

respiratory system
N
• display a rapid increase in peak inspiratory pressure when exposed to high stretch ventilation, as is seen in controls (J:143836)

homeostasis/metabolism
• decreased arterial pO2 after 2 hours of high stretch ventilation
• increased arterial pCO2 after 2 hours of high stretch ventilation

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


Mouse Genome Informatics
hm2
    Tnfrsf1btm1Imx/Tnfrsf1btm1Imx
involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• numbers of microglial cells significantly increased relative to controls after epileptic stimulation
• 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 pulmonary neutrophil accumulation in response to intranasal instillation of M. faeni as compared to control, however monocyte and lymphocyte levels are comparable to control
• increased numbers of T-gamma,delta cells in broncho-alveolar lavage fluid

homeostasis/metabolism
N
• normal recovery after superficial injury causes an increased trans-epidermal water loss (J:59056)
• 41% loss of striatal dopaminergic neurons in MPTP model of Parkinson's disease (controls lose 70%)
• 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
• 41% loss of striatal dopaminergic neurons in MPTP model of Parkinson's disease (controls lose 70%)
• numbers of microglial cells significantly increased relative to controls after epileptic stimulation
• increased glutamate currents

tumorigenesis
• development after DMPA/TPA treatment is reduced

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

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

integument
• development after DMPA/TPA treatment is reduced

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

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Hyperlipidemia, Familial Combined; FCHL 144250 J:45147
NOT Hypertension, Essential 145500 J:45147


Mouse Genome Informatics
cx3
    Birc2tm1.1Rbr/Birc2tm1.1Rbr
Birc3tm1.1Rbr/Birc3tm1.1Rbr
Tnfrsf1btm1Imx/Tnfrsf1btm1Imx

involves: 129S7/SvEvBrd * BALB/cJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging


Mouse Genome Informatics
cx4
    Lepob/Lepob
Tnfrsf1atm1Imx/Tnfrsf1atm1Imx
Tnfrsf1btm1Imx/Tnfrsf1btm1Imx

involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• plasma insulin levels are reduced significantly compared to homozygous Lep mutants
• 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
• 78% reduction in PAI-1 mRNA expression and 80% reduction in TGF-beta gene expression in adipose tissue


Mouse Genome Informatics
cx5
    Tnfrsf1atm1Imx/Tnfrsf1atm1Imx
Tnfrsf1btm1Imx/Tnfrsf1btm1Imx

involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• enhanced survival after caecal ligation and puncture

immune system
• reduced microglial response to excitotoxic injury
• two hours post lipopolysaccharide (LPS) challenge serum levels are 15-20 fold higher than controls, however, TNF kinetics and activity are not altered
• following reverse passive Arthus reaction to induce uveitis, mice exhibit reduced cellular infiltration into the anterior and posterior segments compared with wild-type mice
• do not respond to collagen type II injections as do controls by developing arthritis for at least 14 days
• M. faeni- induced neutrophil accumulation in the lung is decreased as compared to control, however monocyte and lymphocyte levels are comparable to control
• exhibits resistance to a lethal LPS dose plus hepatoxin D-gal (increases sensitivity to LPS)
• 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
• mice have 3 log greater bacterial penetration of the dental pulp eight days after experimental bacterial infection

homeostasis/metabolism
• 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 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
• two hours post lipopolysaccharide (LPS) challenge serum levels are 15-20 fold higher than controls, however, TNF kinetics and activity are not altered
• TNF alpha induced thrombus formation is delayed
• 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
• fail to develop fibroproliferative lesions at bronchiolar-alveolar duct junctions when exposed to chrysotile asbestos fibers
• 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
• 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
• significantly increased area of infarct after middle cerebral artery occlusion

cellular
• 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 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
• 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
• do not respond to collagen type II injections as do controls by developing arthritis for at least 14 days
• 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
• 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
• 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
N
• no overt phenotype when unstressed (J:33864)
• 44% higher level of generalized convulsions in the 2 hours following 1 hour of electrical stimulation in the hippocampus
• significantly increased area of infarct after middle cerebral artery occlusion
• glial response to neuronal injury is blunted
• reduced microglial response to excitotoxic injury
• long term neuron survival in culture is reduced
• 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 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
• reduced food intake at 24 hours but not at 48 hours after caecal ligation and puncture in males
• 44% higher level of generalized convulsions in the 2 hours following 1 hour of electrical stimulation in the hippocampus

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

cardiovascular system
• 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
• 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
• reduced interstitial volume
• more modest development of progressive interstitial fibrosis after uretera; ligation than in controls
• collagen IV deposition
• improved by enalapril treatment

muscle
• 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
• 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
• reduced microglial response to excitotoxic injury

craniofacial
• 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
• 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