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Allele Symbol Allele Name Allele ID |
Lyz2tm1(cre)Ifo targeted mutation 1, Irmgard Forster MGI:1934631 |
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| Summary |
175 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• rare
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• rare
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• rare
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in LPS-treated mice
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• LPS-treated mice exhibit increased survival compared with similarly treated wild-type mice
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• in LPS-treated mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• fewer capillaries per muscle fiber in gastrocnemius after induced hind limb ischemia
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• reduced microvessel formation in sterile sponges implanted subdermally
• reduced VEGF and MMP-9 in sterile sponges implanted subdermally
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• considerable attenuation of blood flow in the gastrocnemius after induced hind limb ischemia
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• higher level of necrosis in the paws of the hind limb at 2 weeks after induced hind limb ischemia
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in response to LPS treatment, mice exhibit increased lethality compared with control mice
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| N |
• mice exhibit normal myelopoiesis
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• enhanced in response to CCR2 signals
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• DSS-treated mice exhibit enhanced progression and maintenance of inflammatory colitis and 2 of 19 mice develop neoplastic transformation in the form of early and late stage colonic epithelial adenomas compared with control mice
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• in response to LPS treatment
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• in response to LPS treatment
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• in response to LPS treatment
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• in response to LPS treatment
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• in response to LPS treatment, mice exhibit increased lethality and increased serum levels of TNF, IL6, IL1B and IL12 compared with control mice
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• 2 of 19 mice DSS-treated develop neoplastic transformation in the form of early and late stage colonic epithelial adenomas compared with control mice
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• mice treated with DSS and DMH exhibit increased incidence, number and size of tumor, mostly adenocarcinomas, compared with control mice
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• 2 of 19 mice DSS-treated develop neoplastic transformation in the form of early and late stage colonic epithelial adenomas compared with control mice
• mice treated with DSS and DMH exhibit increased incidence, number and size of tumor, mostly adenocarcinomas, compared with control mice
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• in mice treated with DSS and DMH
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• 2 of 19 mice DSS-treated develop neoplastic transformation in the form of early and late stage colonic epithelial adenomas compared with control mice
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• mice treated with DSS and DMH exhibit increased incidence, number and size of tumor, mostly adenocarcinomas, compared with control mice
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• DSS-treated mice exhibit enhanced progression and maintenance of inflammatory colitis and 2 of 19 mice develop neoplastic transformation in the form of early and late stage colonic epithelial adenomas compared with control mice
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• in response to LPS treatment
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• in response to LPS treatment
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• in response to LPS treatment
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• in response to LPS treatment
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• in response to LPS treatment, mice exhibit increased lethality compared with control mice
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• 2 of 19 mice DSS-treated develop neoplastic transformation in the form of early and late stage colonic epithelial adenomas compared with control mice
• mice treated with DSS and DMH exhibit increased incidence, number and size of tumor, mostly adenocarcinomas, compared with control mice
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• enhanced in response to CCR2 signals
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• enhanced in response to CCR2 signals
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal susceptibility to MOG induced experimental autoimmune encephalomyelitis and response to treatment with dexamethasone
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in a CASP model of septic peritonitis, mice exhibit reduced circulating CXCL1 compared with control mice
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• in a model of septic peritonitis
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• in a model of septic peritonitis
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• in a model of septic peritonitis
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• in response to septic peritonitis, the peritoneal lavage fluid contains less CXCL10 compared with control mice
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• in a model of septic peritonitis, mice exhibit aggravated liver injury compared with control mice
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| N |
• mice exhibit normal expression of cytokines and neutrophil accumulation in inflammatory models
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• in a CASP model of septic peritonitis, mice exhibit reduced circulating CXCL1 compared with control mice
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• in a model of septic peritonitis
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• in response to septic peritonitis, the peritoneal lavage fluid contains less CXCL10 compared with control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in mice infected with K. pneumonia
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• following cecal ligation and puncture
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• in mice infected with K. pneumonia or following cecal ligation and puncture
• however, response to S. aureus is normal
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• in mice infected with K. pneumonia or following cecal ligation and puncture
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• in peritoneal macrophages from mice stimulated with LPS or K. pneumonia
• however, response to LTA and S. aureus is normal
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• mice infected with K. pneumonia exhibit improved survival, decreased circulating levels of IL6 and TNFalpha, decreased bacterial dissemination and increased neutrophil infiltration compared with control mice
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• in mice infected with K. pneumonia
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• in mice infected with K. pneumonia or following cecal ligation and puncture
• however, response to S. aureus is normal
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• in mice infected with K. pneumonia or following cecal ligation and puncture
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• following cecal ligation and puncture, mice exhibit improved survival, decreased circulating levels of IL6 and TNFalpha, decreased bacterial dissemination and increased neutrophil infiltration compared with control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are resistant to the wasting disease caused by systemic infection with T. gondii
• control mice lose 20% of their body weight by 40 days after T. gondii infection while infected mutant mice have no loss of body weight
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal development and distribution of NK T cells
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• decreased in splenic and liver NK cells after injection of alphaGC
• decreased in splenic NK T cells after injection of alphaGC
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• decreased in splenic and liver NK T cells after injection of alphaGC
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• inguinal adipocytes are smaller in size than controls
• however, in mice fed high fat diet (HFD) the size of visceral adipocytes is similar in both mutant and controls
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• increased amount of epididymal fat
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• HFD-fed mice do not exhibit an impaired freeze response in the fear conditioning assay unlike HFD-fed controls
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• decrease in crown-like structures formed by macrophages in visceral adipose tissue of mice fed HFD as compared to HFD-fed controls
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• decrease in body weight in 5-7 month old mice as compared to controls
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• decrease in snout-anus length
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• delay in fat accumulation on high fat diet (HFD) as compared to controls
• delay in relative loss of lean mass in first 6 weeks of HFD
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• decrease in crown-like structures formed by macrophages in visceral adipose tissue of mice fed HFD as compared to HFD-fed controls
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• delay in fat accumulation on high fat diet (HFD) as compared to controls
• delay in relative loss of lean mass in first 6 weeks of HFD
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• glucose levels are lower in HFD-fed mice as compared to HFD-fed controls
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• insulin levels are lower in HFD-fed mice as compared to HFD-fed controls
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• HDL levels are increased in HFD-fed mice as compared to HFD-fed controls
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• total cholesterol levels are lower in both HFD-fed mice and CD-fed mice as compared to controls
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• LDL cholesterol levels are lower in HFD-fed mice as compared to HFD-fed controls
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• triglyceride levels are lower in HFD-fed mice as compared to HFD-fed controls
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• decrease in crown-like structures formed by macrophages in visceral adipose tissue of mice fed HFD as compared to HFD-fed controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with DSS exhibit a slight reduction of colitis in the early phase compared with control mice
• however, there is no protection after 9 days
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| N |
• mice treated with azoxymethane and dextran sulfate sodium exhibit normal tumorigenesis
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• mice treated with DSS exhibit a slight reduction of colitis in the early phase compared with control mice
• however, there is no protection after 9 days
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in mice treated with diphtheria toxin following injection of carrageenan
• treatment with dexamethasone does not prevent carrageenan-triggered inflammatory-related mechanical hypersensitivity
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• following injection of carrageenan, female and male mice treated with diphtheria toxin exhibit failure to resolve inflammatory mechanical hyperalgesia, thermal hyperalgesia, and posture changes related to inflammatory pain compared with control mice
• mice treated with diphtheria toxin fail to resolve complete Freunds adjuvant-induced transient inflammatory hyperalgesia unlike control mice
• treatment with dexamethasone does not prevent carrageenan-triggered inflammatory-related mechanical hypersensitivity
• macrophages lacking Il4ra, Stat6, or Cd200r1 fail to resolve inflammatory hyperalgesia
• however, carrageenan-induced inflammation is resolved in diphtheria toxin-treated mice and hyperalgesia was rescued by injection of in vitro differentiated bone marrow-derived macrophages and macrophages differentiated with IL-4
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• in mice treated with diphtheria toxin following injection of carrageenan
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after stimulation with heat-killed and PI (propidium iodide)-labeled E. coli for 1 h, peritoneal macrophages endocytose significantly less E. coli than controls macrophages; endocytosed E. coli do not colocalize with Cav1, unlike in control macrophages
• 1 h after infection macrophages show significantly less endocytosis of viable E. coli or S. aureus than control macrophages, as measured by CFUs
• after incubation with Zymosan or latex beads, mean fluorescence intensity of bone marrow-derived macrophages (BMDMs) is significantly lower than that of control macrophages
• upon LPS stimulation, % of surface TLR4 on BMDMs is significantly higher than that on control macrophages, indicating impaired LPS-activated endocytosis of TLR4
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• after exposure to E. coli, the % of live E. coli counts to initially internalized counts is significantly higher than that in control macrophages, suggesting that bactericidal capacity of macrophages is impaired
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• serum IFN-beta levels are significantly reduced at 4 and 8 h after i.p. injection with E. coli
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• serum IL-6 levels are significantly reduced at 4 and 8 h after i.p. injection with E. coli
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• serum TNFalpha levels are significantly reduced at 4 and 8 h after i.p. injection with E. coli
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• upon E. coli or LPS challenge, mice show significantly reduced production of the inflammatory cytokines TNFalpha, IFN-beta, and IL-6 in serum relative to control mice
• upon E. coli or LPS stimulation, macrophages show deceased production of TNFalpha, IFN-beta, and IL-6 relative to control macrophages
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• mice are more susceptible to i.p. E. coli infection with significantly higher bacterial loads in spleen and liver, reduced production of TNFalpha, IFN-beta, and IL-6 in serum, and decreased infiltration of inflammatory cells in lung relative to similarly infected control mice
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• after i.p. injection with E. coli, all mice die by 3 days after challenge whereas most control mice survive to 5 days post infection
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• serum IFN-beta levels are significantly reduced at 4 and 8 h after i.p. injection with E. coli
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• serum IL-6 levels are significantly reduced at 4 and 8 h after i.p. injection with E. coli
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• serum TNFalpha levels are significantly reduced at 4 and 8 h after i.p. injection with E. coli
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• after exposure to E. coli, the % of live E. coli counts to initially internalized counts is significantly higher than that in control macrophages, suggesting that bactericidal capacity of macrophages is impaired
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• after i.p. injection with E. coli, all mice die by 3 days after challenge whereas most control mice survive to 5 days post infection
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• reduction in osteoclast formation
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• mice exhibit a decrease in bone formation rate
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• reduction in osteoclast formation
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• reduction in osteoclast formation
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• reduction in osteoclast formation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• chow-fed mice exhibit a slight but significant reduction in lean mass relative to controls
• however, mice fed a high fat diet (HFD) for 4 weeks show no differences in lean mass relative to HFD-fed controls
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| N |
• chow-fed mice exhibit comparable insulin and glucose tolerance and blood concentrations of glucose and insulin relative to chow-fed controls
• HFD-fed mice show comparable diet-induced obesity with no differences in blood glycerol and free fatty acids (FFA) levels relative to HFD-fed controls
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• upon LPS stimulation, chow-fed mice show significantly reduced blood M1-associated cytokine levels relative to chow-fed control mice
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• upon LPS stimulation, chow-fed mice show significantly reduced blood M1-associated chemokine levels relative to chow-fed control mice
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• hyperinsulinemic-euglycemic clamp studies revealed that mice fed either a regular chow or a HFD show a significantly enhanced steady-state glucose infusion rate, clamp hepatic glucose production, and insulin-stimulated whole-body glucose turnover relative to similarly-fed control mice
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• HFD-fed mice show a significant increase in glucose-induced insulin secretion both in vitro and in vivo relative to HFD-fed controls
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• mice are protected from HFD-induced hyperglycemia, unlike HFD-fed controls
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• mice are protected from HFD-induced hyperinsulinemia, unlike HFD-fed controls
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• HFD-fed mice show significantly reduced gluconeogenesis relative to HFD-fed controls
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• HFD-fed mice show improved glucose tolerance relative to HFD-fed controls
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• hyperinsulinemic-euglycemic clamp studies revealed that mice fed either a regular chow or a HFD show a significantly enhanced whole-body glycogen plus lipid synthesis relative to similarly-fed control mice
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• HFD-fed mice show improved insulin tolerance relative to HFD-fed controls
• hyperinsulinemic-euglycemic clamp studies revealed that increased whole-body insulin sensitivity is due to significant improvements in glucose infusion rates, hepatic insulin action, clamp hepatic glucose production, insulin-stimulated whole body glucose turnover, and whole-body glycogen plus lipid synthesis relative to control mice
• after overnight fasting, HFD-fed mice fail to suppress insulin-stimulated Akt activation in the liver, white adipose tissue and skeletal muscle, unlike similarly treated HFD-fed control mice
• protection of HFD-fed mice against insulin resistance is associated with reduced tissue infiltration by macrophages
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• hyperinsulinemic-euglycemic clamp studies revealed that mice fed either a regular chow or a HFD show a significantly enhanced whole-body glycogen plus lipid synthesis relative to similarly-fed control mice
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• HFD-fed mice show significantly reduced chemokine expression relative to HFD-fed controls
• upon IFN-gamma stimulation, isolated bone marrow-derived macrophages (BMDMs) show decreased expression of chemokine (Ccl2 and Ccl5) genes relative to control BMDMs
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• HFD-fed mice show a significant reduction in pancreatic beta cell proliferation relative to HFD-fed controls
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• HFD-fed mice show a significant reduction in pancreatic islet area relative to HFD-fed controls
• however, chow-fed mice show no differences in islet area relative to chow-fed controls
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• HFD-fed mice show a significant increase in glucose-induced insulin secretion both in vitro and in vivo relative to HFD-fed controls
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• upon IFN-gamma stimulation, isolated bone marrow-derived macrophages (BMDMs) show reduced M1 differentiation and expression of the cell surface marker CD11c relative to control BMDMs
• however, M2 differentiation appears unaffected
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• HFD-fed mice show a significant decrease in the total number of F4/80+ adipose tissue macrophages (ATMs) and reduced accumulation of M1-polarized (F4/80+CD11c+CD206-) ATMs in adipose tissue relative to HFD-fed controls
• HFD-fed mice also show decreased accumulation of M1 tissue macrophages in the liver relative to HFD-fed controls
• HFD-fed mice show no significant difference in the accumulation of M2-polarized ATMs (F4/80+CD11c-CD206+) relative to HFD-fed controls
• chow-fed mice show no differences in total, M1- or M2-polarized ATM number relative to chow-fed controls
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• upon IFN-gamma stimulation, isolated bone marrow-derived macrophages (BMDMs) show decreased expression of M1 marker genes (Ccr7 and Cd11c), chemokines (Ccl2 and Ccl5), and cytokine genes (Il1beta, Il6, and Tnf) relative to control BMDMs
• similar defects are detected in LPS-stimulated macrophages
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• HFD-fed mice show significantly reduced accumulation of M1-polarized (F4/80+CD11c+CD206-) ATMs in adipose tissue relative to HFD-fed controls
• HFD-fed mice show decreased accumulation of M1 tissue macrophages in the liver relative to HFD-fed controls
• however, HFD-fed mice show no significant difference in the accumulation of M2-polarized ATMs (F4/80+CD11c-CD206+) relative to HFD-fed controls
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• upon IFN-gamma stimulation, isolated BMDMs show decreased expression of cytokine genes (Il1beta, Il6, and Tnf) relative to control BMDMs
|
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• upon LPS stimulation, chow-fed mice show significantly reduced blood M1-associated cytokine levels relative to chow-fed control mice
|
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• upon LPS stimulation, chow-fed mice show significantly reduced blood M1-associated chemokine levels relative to chow-fed control mice
|
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• HFD-fed mice show significantly reduced chemokine expression relative to HFD-fed controls
• upon IFN-gamma stimulation, isolated bone marrow-derived macrophages (BMDMs) show decreased expression of chemokine (Ccl2 and Ccl5) genes relative to control BMDMs
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• HFD-fed mice show significantly reduced hepatic inflammation relative to HFD-fed controls
|
|
• upon IFN-gamma stimulation, isolated bone marrow-derived macrophages (BMDMs) show reduced M1 differentiation and expression of the cell surface marker CD11c relative to control BMDMs
• however, M2 differentiation appears unaffected
|
|
• HFD-fed mice show a significant decrease in the total number of F4/80+ adipose tissue macrophages (ATMs) and reduced accumulation of M1-polarized (F4/80+CD11c+CD206-) ATMs in adipose tissue relative to HFD-fed controls
• HFD-fed mice also show decreased accumulation of M1 tissue macrophages in the liver relative to HFD-fed controls
• HFD-fed mice show no significant difference in the accumulation of M2-polarized ATMs (F4/80+CD11c-CD206+) relative to HFD-fed controls
• chow-fed mice show no differences in total, M1- or M2-polarized ATM number relative to chow-fed controls
|
|
• upon IFN-gamma stimulation, isolated bone marrow-derived macrophages (BMDMs) show decreased expression of M1 marker genes (Ccr7 and Cd11c), chemokines (Ccl2 and Ccl5), and cytokine genes (Il1beta, Il6, and Tnf) relative to control BMDMs
• similar defects are detected in LPS-stimulated macrophages
|
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• HFD-fed mice show significantly reduced accumulation of M1-polarized (F4/80+CD11c+CD206-) ATMs in adipose tissue relative to HFD-fed controls
• HFD-fed mice show decreased accumulation of M1 tissue macrophages in the liver relative to HFD-fed controls
• however, HFD-fed mice show no significant difference in the accumulation of M2-polarized ATMs (F4/80+CD11c-CD206+) relative to HFD-fed controls
|
|
• upon IFN-gamma stimulation, isolated BMDMs show decreased expression of cytokine genes (Il1beta, Il6, and Tnf) relative to control BMDMs
|
|
• upon IFN-gamma stimulation, isolated bone marrow-derived macrophages (BMDMs) show reduced M1 differentiation and expression of the cell surface marker CD11c relative to control BMDMs
• however, M2 differentiation appears unaffected
|
|
• HFD-fed mice show significantly reduced accumulation of M1-polarized (F4/80+CD11c+CD206-) ATMs in adipose tissue relative to HFD-fed controls
• HFD-fed mice show decreased accumulation of M1 tissue macrophages in the liver relative to HFD-fed controls
• however, HFD-fed mice show no significant difference in the accumulation of M2-polarized ATMs (F4/80+CD11c-CD206+) relative to HFD-fed controls
|
|
• HFD-fed mice show a significant reduction in pancreatic beta cell proliferation relative to HFD-fed controls
|
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• bone formation rate with prednisolone treatment for 2 weeks is reduced in mutants and controls
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|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in draining lymph node cells from collagen-treated wild-type mice
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• myeloid cells from collage-treated mice exhibit increased CXCL1 and CXCL2 production compared with wild-type mice
|
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• in draining lymph node cells from collagen-treated wild-type mice
• in myeloid cells from the ankles of collagen-treated mice
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• in myeloid cells from the ankles of collagen-treated mice
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• in draining lymph node cells from collagen-treated wild-type mice
• in myeloid cells from the ankles of collagen-treated mice
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• in myeloid cells from the ankles of collage-treated mice
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• collagen treated mice exhibit earlier and more severe arthritis with increased number of paws affected, inflammation, cartilage erosion, and neutrophil infiltration compared with similarly treated wild-type mice
• draining lymph node cells from collagen-stimulated mice exhibit increased T cell proliferation, and IFN-gamma and IL17 production compared with similarly treated wild-type cells
• myeloid cells from the ankles of collagen-treated mice exhibit increased IL1b, IL6, IFNgamma, IL17, CXCL1, and CXCL2 production compared with wild-type mice
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• collagen treated mice exhibit earlier and more severe arthritis with increased number of paws affected, inflammation, cartilage erosion, and neutrophil infiltration compared with similarly treated wild-type mice
• draining lymph node cells from collagen-stimulated mice exhibit increased T cell proliferation, and IFN-gamma and IL17 production compared with similarly treated wild-type cells
• myeloid cells from the ankles of collagen-treated mice exhibit increased IL1b, IL6, IFNgamma, IL17, CXCL1, and CXCL2 production compared with wild-type mice
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• in draining lymph node cells from collagen-treated wild-type mice
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• in draining lymph node cells from collagen-treated wild-type mice
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|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Hmox1tm1.1Gkl/Hmox1tm1.1Gkl Lyz2tm1(cre)Ifo/Lyz2+ mice show decreased susceptibility to L. monocytogenes infection
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• mice infected with L. monocytogenes and treated with polyI:C exhibit decreased IFN-beta production and mortality compared to similarly treated wild-type mice
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• MOG-treated mice exhibit a 4-fold increase in splenocyte proliferation compared to similarly treated wild-type mice
|
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• in MOG-treated mice
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• in MOG-treated mice
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• MOG-treated mice exhibit an increase in CD4+ T cells compared to in similarly treated wild-type mice
• MOG-treated mice exhibit a 5-fold increase in the number of IL17-producing CD4+ T cells and a 2-fold increase in IFN-gamma-producing CD4+ T cells compared to similarly treated wild-type mice
|
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• in MOG-treated mice
|
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• in MOG-treated mice
|
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• MOG-treated mice exhibit increased IFN-gamma and TNF serum levels compared to similarly treated wild-type mice
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• polyI:C- or LPS-stimulated macrophages or mice stimulated with LPS and infected with L. monocytogenes produce less IFN-beta than similarly treated wild-type cells or mice
• macrophages infected with the Sendai virus produce less IFN-beta than similarly treated wild-type cells
|
|
• MOG-treated mice exhibit increased IFN-gamma and TNF serum levels compared to similarly treated wild-type mice
|
|
• mice exhibit exacerbated experimental autoimmune encephalomyelitis (EAE) and do not exhibit suppression of EAE symptoms and IFN-beta production by polyI:C treatment unlike similarly treated wild-type mice
• MOG-treated mice exhibit a 4-fold increase in splenocyte proliferation compared to similarly treated wild-type mice
• MOG-treated mice exhibit increased IFN-gamma and TNF serum levels compared to similarly treated wild-type mice
• MOG-treated mice exhibit more cellular infiltration with increased CD4+ and CD8+ T cells, macrophages, B cells, and granulocytes and increased demyelination throughout the spinal cord compared to similarly treated wild-type mice
• MOG-treated mice exhibit a 5-fold increase in the number of IL17-producing CD4+ T cells and a 2-fold increase in IFN-gamma-producing CD4+ T cells compared to similarly treated wild-type mice
|
|
• mice infected with L. monocytogenes and treated with polyI:C exhibit decreased IFN-beta production and mortality compared to similarly treated wild-type mice
|
|
• macrophages infected with the Sendai virus produce less IFN-beta than similarly treated wild-type cells
|
|
• MOG-treated mice exhibit increased IFN-gamma and TNF serum levels compared to similarly treated wild-type mice
|
|
• MOG-treated mice exhibit a 4-fold increase in splenocyte proliferation compared to similarly treated wild-type mice
|
|
• in MOG-treated mice
|
|
• in MOG-treated mice
|
|
• MOG-treated mice exhibit an increase in CD4+ T cells compared to in similarly treated wild-type mice
• MOG-treated mice exhibit a 5-fold increase in the number of IL17-producing CD4+ T cells and a 2-fold increase in IFN-gamma-producing CD4+ T cells compared to similarly treated wild-type mice
|
|
• in MOG-treated mice
|
|
• in MOG-treated mice
|
|
• MOG-treated mice exhibit a 4-fold increase in splenocyte proliferation compared to similarly treated wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased degranulation
|
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• increased degranulation
|
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• in serum after renal ischemia-reperfusion experiments
|
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• increased degranulation
|
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• increased degranulation
|
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• after renal ischemia-reperfusion experiments
|
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• after renal ischemia-reperfusion experiments
|
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• died within 4 days after Listeria monocytogenes infection whereas controls survived
|
|
• serum TNF levels were dramatically reduced in mutants injected with LPS, with TNF production decreased by 100-fold in macrophages
|
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• induction of MCP-1 was reduced in spleens of mutants infected with Listeria monocytogenes
|
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• increased resistance to liver injury after ConA-induced autoimmune hepatitis
|
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• fully resistant to lipopolysaccharide (LPS)/D-Gal induced septic shock
• protected from toxic shock induced by enterotoxin B, a superantigen from S. aureus
|
|
• loss of resistance against Listeria monocytogenes, developing uncontrolled infection, leading to death within 4 days and a 3-4 log increase in bacterial load in the liver and spleen
|
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• mutants infected with Listeria monocytogenes developed large, confluent inflammatory necrotic areas with many Mac-1 and Gr1-positive cells
• no liver necrosis, only infiltrating cells, were detected in mutants with ConA induced autoimmune hepatitis
|
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• serum TNF levels were dramatically reduced in mutants injected with LPS, with TNF production decreased by 100-fold in macrophages
|
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• mutants infected with Listeria monocytogenes developed large, confluent inflammatory necrotic areas with many Mac-1 and Gr1-positive cells
• no liver necrosis, only infiltrating cells, were detected in mutants with ConA induced autoimmune hepatitis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no elevation of expression of major histocompatibility complex (MHC) class II peptides on surface of resident peritoneal macrophages
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• LPS-induced alternative pathway (AP) complement activation is impaired unlike in wild-type mice
|
|
|
• in a K/BxN model
|
|
|
• in a K/BxN model
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following wire injury, mice exhibit decreased intima to media ratio and stenosis percent with increased leukocyte recruitment compared with control mice
|
|
• decreased LPS-stimulated prostaglandin E2
• however, LPS-stimulated prostaglandin D2 levels are normal
|
|
• increased LPS-stimulated prostaglandin I2 levels
|
|
• increased leukocyte recruitment following wire injury
|
|
• increased leukocyte recruitment following wire injury
|
|
• following wire injury, mice exhibit decreased intima to media ratio and stenosis percent with increased leukocyte recruitment compared with control mice
|
|
• increased leukocyte recruitment following wire injury
|
|
• increased leukocyte recruitment following wire injury
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• neutrophils exhibit an unusual hypermature morphology characterized by nuclear hypersegmentation and blebbing
|
|
|
• neutrophil numbers are normal in these mice unlike the increased numbers observed in Mirn223tm1Fcam homozygotes
|
|
|
• neutorphils are hypersensitive to activating stimuli
• neutrophils have higher oxidative burst than controls upon low-dose PMA stimulation
• neutrophils display higher killing when co-cultured with Candida albicans
|
|
|
• neutrophils exhibit an unusual hypermature morphology characterized by nuclear hypersegmentation and blebbing
|
|
|
• neutrophil numbers are normal in these mice unlike the increased numbers observed in Mirn223tm1Fcam homozygotes
|
|
|
• neutorphils are hypersensitive to activating stimuli
• neutrophils have higher oxidative burst than controls upon low-dose PMA stimulation
• neutrophils display higher killing when co-cultured with Candida albicans
|
|
|
• neutrophils exhibit an unusual hypermature morphology characterized by nuclear hypersegmentation and blebbing
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• postnatal lethality does not occur to mice on a IL-1 receptor null background
|
|
• variable skin inflammation is observed
|
|
• variable skin inflammation is observed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice appear phenotypically normal and do not develop the inflammatory disease that conditional heterozygotes develop on an intact Pycard background
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice treated with dextran sodium sulfate (DSS) to induce colitis show similar colitis-induced injury as controls, with slightly greater weight loss but similar colon shortening and splenic enlargement
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants are more resistant to LPS induced endotoxin shock
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die between 2 and 14 days after birth probably due to multisystem organ failure secondary to inflammation and necrosis
• genotype demonstrates inflammatory disease of the conditional allele does not require presence of wild-type allele
|
|
• mice have pronounced leukocytic infiltrates in skin, liver, spleen, joint, sinus, conjunctiva, bone marrow, and tongue that are mainly neutrophilic
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• only 6.2% of bone marrow derived macrophages express MHC-II on the surface compared to 30% of controls
• incubation with IFN-gamma increases percentage to 19% which is much less than 72% of wild-type macrophages
|
|
• only 6.2% of bone marrow derived macrophages express MHC-II on the surface compared to 30% of controls
• incubation with IFN-gamma increases percentage to 19% which is much less than 72% of wild-type macrophages
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• during the early and middle phases of wound healing, mice exhibit reduced formation and vascularization of granulation tissue compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• normal numbers of peritoneal macrophage
• no CTP:phosphocholine cytidylyltransferase alpha produced
• CTP:phosphocholine cytidylyltransferase, beta isoform upregulated
• severely reduced conversion of free cholesterol to phosphatidylcholine
• increased free cholesterol load leads to macrophage cell death
|
|
• normal numbers of peritoneal macrophage
• no CTP:phosphocholine cytidylyltransferase alpha produced
• CTP:phosphocholine cytidylyltransferase, beta isoform upregulated
• severely reduced conversion of free cholesterol to phosphatidylcholine
• increased free cholesterol load leads to macrophage cell death
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• bone marrow derived macrophage show increased levels of LPS induced IL-10 mRNA and no further effect from addition PGE2 stimulation
|
|
• bone marrow derived macrophage show increased levels of LPS induced IL-10 mRNA and no further effect from addition PGE2 stimulation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice infected with HSV-1 exhibit increased mortality compared to controls
|
| N |
• mice show similar frequencies of F4/80+CD11b+ macrophages, natural killer cells, B cells, T cells, neutrophils, and monocytes in the spleen as in wild-type mice
|
|
• peritoneal macrophages infected with vaccinia virus (VACV) induces IFNB1 production to a certain level after 4 hours but shows no subsequent increases as seen in wild-type peritoneal macrophages
• macrophages infected with vaccinia virus show lower and less sustained IFNB1 expression than wild-type macrophages
|
|
• HSV-1 challenged mice exhibit severely attenuated serum IFN-beta concentrations
• however, serum IL-6, IFN-beta, and TNF-alpha concentrations are similar to wild-type mice after RNA virus Sendai virus infection
|
|
• HSV-1 infected peritoneal macrophages show decreased secretion of IFN-beta
|
|
• mice infected with herpes simplex type 1 virus (HSV-1)
|
|
• mice infected with HSV-1 exhibit increased mortality compared to controls
|
|
• peritoneal macrophages infected with vaccinia virus (VACV) induces IFNB1 production to a certain level after 4 hours but shows no subsequent increases as seen in wild-type peritoneal macrophages
• macrophages infected with vaccinia virus show lower and less sustained IFNB1 expression than wild-type macrophages
|
|
• HSV-1 challenged mice exhibit severely attenuated serum IFN-beta concentrations
• however, serum IL-6, IFN-beta, and TNF-alpha concentrations are similar to wild-type mice after RNA virus Sendai virus infection
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice appear normal at weaning but fail to gain weight
|
|
• increase in levels of circulating neutrophils
|
|
• increase in levels of circulating lymphocytes
|
|
• increase in levels of circulating monocytes
|
|
• spleens show increased expression of interferon signature genes such as Ddx58 and Isg95
|
|
• IgG deposition in the glomeruli of kidneys
|
|
• macrophages exhibit an acute elevation of proinflammatory cytokines IL-1beta, IL-6, and IP-10, but not IL-10, in response to ingesting dying cells that is not seen in control macrophages
• however, neither bone marrow-derived macrophages nor peritoneal exudate macrophages from 52 week old mice show any defects in the engulfment of dying cells in vitro indicating normal phagocytic capacity
|
|
• levels of CXCL1, CCL4 and CCL2 are increased in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• increase in levels of circulating neutrophils
|
|
• increase in levels of circulating lymphocytes
|
|
• increase in levels of circulating monocytes
|
|
• spleens show increased expression of interferon signature genes such as Ddx58 and Isg95
|
|
• IgG deposition in the glomeruli of kidneys
|
|
• macrophages exhibit an acute elevation of proinflammatory cytokines IL-1beta, IL-6, and IP-10, but not IL-10, in response to ingesting dying cells that is not seen in control macrophages
• however, neither bone marrow-derived macrophages nor peritoneal exudate macrophages from 52 week old mice show any defects in the engulfment of dying cells in vitro indicating normal phagocytic capacity
|
|
• levels of CXCL1, CCL4 and CCL2 are increased in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• mice develop a systemic lupus erythematosus-like disease (SLE)
|
|
• increase in serum levels of a broad array of antibodies against autoantigens commonly associated with SLE
|
|
• kidneys from aged mice show endocapillary proliferative glomerulonephritis
|
|
• mice show indications of kidney damage and show increased functional markers of kidney injury
|
|
• IgG and complement C1q deposition in the glomeruli of kidneys
|
|
• kidneys from aged mice show endocapillary proliferative glomerulonephritis
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| systemic lupus erythematosus | DOID:9074 |
OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420 |
J:235399 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal myeloid lineage and in vitro M1 and M2 macrophage differentiation
|
|
• decrease in autophagosome formation in response to lipopolysaccharide injection or bacterial infection
|
|
• with TLR stimulation and pan-caspase inhibition treatments
|
|
• decrease in generation of LC3-II by peritonela macrophages following infection with L. monocytogenes indicates impaired induction of autophagy
|
|
• decrease in autophagosome formation in response to lipopolysaccharide injection or bacterial infection
|
|
• with TLR stimulation and pan-caspase inhibition treatments
|
|
• decrease in generation of LC3-II by peritonela macrophages following infection with L. monocytogenes indicates impaired induction of autophagy
|
|
• elevated levels of Il1 beta and IL18 in LPS stimulated mice suggest hyperactivation of the inflammasome pathway
|
|
• elevated levels of Il1 beta and IL18 in LPS stimulated mice suggest hyperactivation of the inflammasome pathway
|
|
• in cultured macrophages stimulated with LPS and ATP
|
|
• in cultured macrophages stimulated with LPS and ATP
|
|
• along with massive lung tissue destruction upon lipopoysaccharide injection
|
|
• elevated levels of Il1 beta and IL18 in LPS stimulated mice suggest hyperactivation of the inflammasome pathway
|
|
• elevated levels of Il1 beta and IL18 in LPS stimulated mice suggest hyperactivation of the inflammasome pathway
|
|
• higher in vitro macrophage cell death after lipopolysaccharide injection
|
|
• with TLR stimulation and pan-caspase inhibition treatments
|
|
• decrease in generation of LC3-II by peritonela macrophages following infection with L. monocytogenes indicates impaired induction of autophagy
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increase in mortality after injection with high dose LPS (30 mg/kg)
|
|
• increased weight loss, higher colitis scores, and shorter colonic lengths following DSS induced colitis
|
|
• primary peritoneal macrophages show higher TNF-alpha and IL6 expression and secretion following stimulation with LPS, PGN, or poly(I:C)
|
|
• 4h after LPS stimulation
|
|
• 4h after LPS stimulation
|
|
• increase in infiltration of immune cells and more severe injuries after LPS treatment
|
|
• increase in mortality after injection with high dose LPS (30 mg/kg)
|
|
• increased weight loss, higher colitis scores, and shorter colonic lengths following DSS induced colitis
|
|
• 4h after LPS stimulation
|
|
• 4h after LPS stimulation
|
|
• primary peritoneal macrophages show higher TNF-alpha and IL6 expression and secretion following stimulation with LPS, PGN, or poly(I:C)
|
|
• increase in infiltration of immune cells and more severe injuries after LPS treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice fed standard chow or a high fat diet exhibit normal body weight and composition
|
| N |
• mice fed standard chow or a high fat diet exhibit normal glucose tolerance
|
| N |
• brown adipose tissue exhibits normal mitochondrial function (measured by cox activity)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• TNF levels in the serum of mice expressing Cre are lower by more than two thirds compared to controls 3 hours after LPS injection
|
|
• LPS stimulated release of TNF from macrophages is strongly reduced in these mice
|
|
• TNF levels in the serum of mice expressing Cre are lower by more than two thirds compared to controls 3 hours after LPS injection
|
|
• two weeks after induction of Cre recombinase, mice are more resistant to endotoxin shock than in controls
• 10 of 13 mice survive endotoxin induction with LPS and D-galactosamine while 11 of 13 controls die within 8 hours of injection
|
|
• LPS stimulated release of TNF from macrophages is strongly reduced in these mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased migration into CNS in myelin oligodendrocyte glycoprotein MOG-CFA-induced EAE experiments
|
|
• significantly increased ROS production from CNS-infiltrating leukocytes in MOG-CFA-induced EAE experiments
• significantly increased malondialdehyde levels in CNS tissue in MOG-CFA-induced EAE experiments
|
|
• increased migration into CNS in myelin oligodendrocyte glycoprotein MOG-CFA-induced EAE experiments
|
|
• increased migration into CNS in myelin oligodendrocyte glycoprotein MOG-CFA-induced EAE experiments
|
|
• increased disease severity (lesions in central nervous system (CNS)) and high mortality in myelin oligodendrocyte glycoprotein (MOG)35-55-complete Freunds adjuvant (CFA)-induced EAE experiments
• when treated with reactive oxygen species (ROS) scavengers after EAE induction with MOG-CFA
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 50% mortality before 32 weeks of age
• mortality increases to 80% by 3-5 weeks if Lyz2tm1(cre)Ifo is homozygous
|
|
• 50% reduction in body size
|
|
• splenomegaly with loss of lymphoid follicles
• normal cell number but composition includes more large immature and myeloid cells and fewer lymphocytes
|
|
• increased number of neutrophiles
• decrease in thymocytes
|
|
• loss of a distinct medulla and cortex
|
|
• reduced bone marrow erythropoiesis
|
|
• splenic extramedullary myelopoiesis
|
|
• expanded number of neutrophiles
• reduced erythropoiesis
|
|
• thrombocytosis
|
|
• decreased percentage but not in absolute numbers in peripheral blood
• absolute number of B cells reduced in the spleen
|
|
• decreased percentage but not in absolute numbers in peripheral blood
|
|
• decreased percentage in peripheral blood
|
|
• slightly increased in absolute numbers in peripheral blood
|
|
• reduced numbers in the peritoneal cavity
|
|
• 5 fold increase in leukocytes in peripheral blood
|
|
• increased more than 10 fold
• accumulate in the lung alveolar spaces and around the large blood vessels
• accumulate in the small intestine, particularly the jejunum
• increased numbers in the peritoneal cavity
|
|
• increased more than 10 fold
• increase of the inflammatory subclass
|
|
• disrupted architecture
• granulocyte infiltration
• infiltration of neutrophiles
|
|
• splenomegaly with loss of lymphoid follicles
• normal cell number but composition includes more large immature and myeloid cells and fewer lymphocytes
|
|
• reduction in macrophage number
|
|
• loss of lymphoid follicles
|
|
• reduction in macrophage number
|
|
• increased number of neutrophiles
• decrease in thymocytes
|
|
• loss of a distinct medulla and cortex
|
|
• splenic extramedullary myelopoiesis
|
|
• decreased percentage but not in absolute numbers in peripheral blood
• absolute number of B cells reduced in the spleen
|
|
• decreased percentage but not in absolute numbers in peripheral blood
|
|
• decreased percentage in peripheral blood
|
|
• slightly increased in absolute numbers in peripheral blood
|
|
• reduced numbers in the peritoneal cavity
|
|
• 5 fold increase in leukocytes in peripheral blood
|
|
• increased more than 10 fold
• accumulate in the lung alveolar spaces and around the large blood vessels
• accumulate in the small intestine, particularly the jejunum
• increased numbers in the peritoneal cavity
|
|
• increased more than 10 fold
• increase of the inflammatory subclass
|
|
• disrupted architecture
• granulocyte infiltration
• infiltration of neutrophiles
|
|
• splenomegaly with loss of lymphoid follicles
• normal cell number but composition includes more large immature and myeloid cells and fewer lymphocytes
|
|
• reduction in macrophage number
|
|
• loss of lymphoid follicles
|
|
• reduction in macrophage number
|
|
• loss of lymphoid follicles
• infiltration of neutrophiles
• 4fewer macrophage
|
|
• increased number of neutrophiles
• decrease in thymocytes
|
|
• loss of a distinct medulla and cortex
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen treated mice do not develop arteriovenous malformations in response to AAV-VEGF injection into the basal ganglia at 8-10 weeks of age or around the ear tag wound
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• to the inflamed endothelium
|
|
• during TNF-alpha-induced inflammation, mice exhibit increased rolling influx, reduced percentage of crawling cells among adherent neutrophils and reduced number of adherent neutrophils to the inflamed endothelium
• neutrophils exhibit reduced neutrophil adhesion to ICAM-1-coated surface compared with wild-type cells
|
|
• to the inflamed endothelium
|
|
• during TNF-alpha-induced inflammation, mice exhibit increased rolling influx, reduced percentage of crawling cells among adherent neutrophils and reduced number of adherent neutrophils to the inflamed endothelium
• neutrophils exhibit reduced neutrophil adhesion to ICAM-1-coated surface compared with wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• display increased bacterial titers in the blood and feces
• despite this mice survive the infection
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal perinatal survival
|
| N |
• mice exhibit normal lymphatic vessels with normal integrity
|
| N |
• mice do not exhibit edema
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not develop lupus-like disease and do not exhibit an increase in anti-double stranded DNA antibodies or in anti-nuclear antibodies, do not show glomerular immune complex deposition, show normal serum creatinine levels and cytokine levels, and normal clearance of engulfed, dying cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD44hi myeloid cells fail to promote repair of oxygen-induced retinopathy unlike wild-type cells
|
|
• macrophages exhibit impaired glycolysis and energy generation compared with wild-type cells
• bacteria exposed macrophages contain 7-fold more viable bacteria than similarly treated wild-type mice
• macrophages lack homotypic adhesion unlike wild-type cells
|
|
• macrophage capacity to invade matrigel is severely defective compared with wild-type mice
• macrophage migration through artificial extracellular matrix is decreased 60% compared with wild-type cells
• macrophage exhibit reduced directed motility in the absence of matrigel by 50% at normoxia and 75% under hypoxic conditions compared with similarly treated wild-type cells
|
|
• in LPS-treated macrophages
|
|
• TPA-treated ears exhibit reduced inflammatory infiltration and edema compared with similarly treated wild-type cells
• following disruption of barrier function with 5% SDS (chronic cutaneous inflammation), mice fail to exhibit an inflammatory response as in similarly treated wild-type mice
|
|
• following oxygen-induced retinopathy, mice exhibit decreased repair of retinal damage compared with similarly treated wild-type mice
• CD44hi myeloid cells fail to promote repair of oxygen-induced retinopathy unlike wild-type cells
|
|
• macrophage capacity to invade matrigel is severely defective compared with wild-type mice
• macrophage migration through artificial extracellular matrix is decreased 60% compared with wild-type cells
• macrophage exhibit reduced directed motility in the absence of matrigel by 50% at normoxia and 75% under hypoxic conditions compared with similarly treated wild-type cells
|
|
• CD44hi myeloid cells fail to promote repair of oxygen-induced retinopathy unlike wild-type cells
|
|
• macrophages exhibit impaired glycolysis and energy generation compared with wild-type cells
• bacteria exposed macrophages contain 7-fold more viable bacteria than similarly treated wild-type mice
• macrophages lack homotypic adhesion unlike wild-type cells
|
|
• macrophage capacity to invade matrigel is severely defective compared with wild-type mice
• macrophage migration through artificial extracellular matrix is decreased 60% compared with wild-type cells
• macrophage exhibit reduced directed motility in the absence of matrigel by 50% at normoxia and 75% under hypoxic conditions compared with similarly treated wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in LPS-treated mice compared with similarly treated wild-type mice
|
|
• 4 hours after LPS treatment
|
|
• 4 hours after LPS treatment
|
|
• 4 hours after LPS treatment
|
|
• 1.5 hrs after LPS treatment
|
|
• 1.5 and 4 hrs after LPS treatment
|
|
• LPS-treated mice exhibit less hypothermia, hypotension, and mortality; improved hemodynamic parameter, shock index, and heart rate to systolic blood pressure; and decreased macrophage cytokine production (TNF-alpha, IL6, IL12, IL1a, and IL1b) compared with similarly treated wild-type mice
|
|
• LPS-treated mice develop less hypothermia compared with similarly treated wild-type mice
|
|
• in LPS-treated mice compared with similarly treated wild-type mice
|
|
• LPS-treated mice develop less hypotension compared with similarly treated wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice show normal weight gain at 10 weeks of age
|
|
• slight increase in IFN-gamma levels
|
|
• slight increase in IL-6 levels
|
|
• slight increase in TNF levels
|
| N |
• mice show no joint inflammation at 10 weeks of age, cytokine levels (such as IL-1 alpha, IL-1 beta, and MCP-1) are severely reduced, and the autoinflammatory disease seen in Gt(ROSA)26Sortm1(OVAL/fla-GFP)Vnce and Lyz2tm1(cre)Ifo expressing mice is almost entirely ameliorated
|
|
• slight increase in IFN-gamma levels
|
|
• slight increase in IL-6 levels
|
|
• slight increase in TNF levels
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tissue glucocerebrosidase activity is reduced to ~30-50% of control levels in all tissues
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal Th1 responses and do not develop colitis, unlike Stat3 null mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• an increased frequency of granulocyte-monocyte progenitors in the bone marrow
|
|
• bone marrow cells demonstrate a significant increase in both mature myeloid, immature myeloid and monocytic cells
|
|
• a decreased frequency of megakaryocyte-erythroid progenitors
|
|
• a decreased frequency of megakaryocyte-erythroid progenitors
|
|
• show a 2-fold increase in the numbers of circulating monocytes at 5 to 7 months of age
|
|
• bone marrow cells demonstrate a significant increase in both mature myeloid, immature myeloid and monocytic cells
|
|
• show a 2-fold increase in the numbers of circulating monocytes at 5 to 7 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in ovariectomized mice treated with 17beta-estradiol due to reduced re-epithelialization of the wound
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• S. aureus-infected mice exhibit an increased in viable S. aureus compared to in similarly treated wild-type mice
|
|
• S. aureus-infected mice exhibit an increased in viable S. aureus compared to in similarly treated wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• migration of neutrophils to the cite of bacterial infection is enhanced compared to in similarly treated wild-type mice
|
|
• S. aureus-infected mice exhibit a 3- to 4-fold increased in viable S. aureus compared to in similarly treated wild-type mice
|
|
• migration of neutrophils to the cite of bacterial infection is enhanced compared to in similarly treated wild-type mice
|
|
• S. aureus-infected mice exhibit a 3- to 4-fold increased in viable S. aureus compared to in similarly treated wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• osteoclasts exhibit decreased fusion during differentiation
|
|
• decreased size of multinucleate osteoclasts as compared to controls
• osteoclasts exhibit decreased fusion during differentiation
|
|
• osteoclasts exhibit decreased fusion during differentiation
|
|
• numbers of osteoclasts are decreased during differentiation
|
|
• decreased levels of serum type I collagen as compared to wild type
|
|
• decreased size of multinucleate osteoclasts as compared to controls
• osteoclasts exhibit decreased fusion during differentiation
|
|
• osteoclasts exhibit decreased fusion during differentiation
|
|
• numbers of osteoclasts are decreased during differentiation
|
|
• decreased size of multinucleate osteoclasts as compared to controls
• osteoclasts exhibit decreased fusion during differentiation
|
|
• osteoclasts exhibit decreased fusion during differentiation
|
|
• numbers of osteoclasts are decreased during differentiation
|
|
• increased bone mineral density is found in 2 and 6 month old mice as compared to controls
|
|
• increased trabecular bone volume in femoral and tibial bones
|
|
• macrophage infiltration is decreased in implanted subcutaneous tumors as compared to tumor implanted controls
|
|
• implanted melanoma cells have an increased live cell mass and volume as compared to tumor implanted controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• macrophages exhibit impaired ability to phagocytose and remove apoptotic cells
|
|
• mice develop colitis similar to Itgavtm2Hyn/Itgavtm2.1Hyn;Tg(Tek-cre)1Ywa mice with similar histology and proinflammatory cytokine expression but at a lower rate (30% compared to 100% of Itgavtm2Hyn/Itgavtm2.1Hyn;Tg(Tek-cre)1Ywa mice at 40 weeks)
|
|
• mice contain higher levels of autoantibodies including ones against tropomyosin, phosphotidylserine, double-stranded DNA and anti-nuclear antibodies compared to in Itgavtm2Hyn heterozygote controls
|
|
• mice develop colitis similar to Itgavtm2Hyn/Itgavtm2.1Hyn;Tg(Tek-cre)1Ywa mice with similar histology and proinflammatory cytokine expression but at a lower rate (30% compared to 100% of Itgavtm2Hyn/Itgavtm2.1Hyn;Tg(Tek-cre)1Ywa mice at 40 weeks)
|
|
• macrophages exhibit impaired ability to phagocytose and remove apoptotic cells
|
|
• macrophages exhibit impaired ability to phagocytose and remove apoptotic cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normally differentiating T, B, and myeloid cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• macrophage recruitment to inflamed lungs is increased
|
|
• number of resident alveolar macrophages in unchallenged mutants is increased by more than 60% percent compared to wild-type
|
|
• neutrophils isolated from bone marrow live longer than wild-type neutrophils
(J:114699)
• neutrophils exhibit enhanced ruffling in response to the chemoattractant fMLP or IL-8
(J:145331)
• polarized neutrophils exhibit a considerable increase in multiple pseudopodia compared to wild-type mice
(J:145331)
• neutrophils show more diffuse F-actin localization at the leading edge or pseudopodia than wild-type neutrophils
(J:145331)
• fMLP-stimulated, but not PMA-stimulated, neutrophils exhibit increased and prolonged superoxide production compared to wild-type neutrophils
(J:145331)
• neutrophils exhibit enhanced transwell chemotaxis toward fMLP, IL-8 or C5a
(J:145331)
• neutrophils are more active and move faster than wild-type neutrophils but lack some of the directionality of wild-type neutrophils
(J:145331)
• in a model of peritonitis, neutrophil recruitment at sites of inflammation is increased in mutants compared to wild-type mice
(J:145331)
• in a model of bacterial pneumonia, apoptosis of lung recruited neutrophils is reduced in mutants compared to wild-type mice
(J:148947)
• neutrophils exhibit enhanced bacteria-killing capacity in a model of bacterial pneumonia
(J:148947)
• neutrophils have an increased phagocytic index compared to wild-type in a model of bacterial pneumonia
(J:148947)
• neutrophils exhibit enhanced E.coli and zymosan-induced phagocytosis-associated superoxide production
(J:148947)
|
|
• in a bacterial pneumonia model in which mutants are intratracheally infected with E.coli to induce lung inflammation, mutants exhibit an increase in bacteria-induced neutrophil recruitment compared to controls
• mutants treated with the chemotherapeutic drug, cyclophosphamide, to induce neutropenia, exhibit fewer neutrophils in the lungs than untreated mutants, but more neutrophils than drug treated wild-type mice
|
|
• increase in cytokine/chemokine concentrations in inflamed lungs of E.coli infected mutants due to increased numbers of resident alveolar macrophages and not due to enhanced capability of macrophages to produce cytokines or chemokines
|
|
• mutants develop more severe lung inflammation in response to bacterial pneumonia than controls
|
|
• induction of neutropenia in mutants with the chemotherapeutic drug, cyclophosphamide, results in enhanced neutrophil accumulation in the lungs leading to better clearance of instilled bacteria and accelerated resolution of bacteria-induced lung inflammation
|
|
• mutants made neutropenic with the chemotherapeutic drug, cyclophosphamide, exhibit decreased mortality after E.coli challenge compared to wild-type mice due to enhanced neutrophil accumulation in the lungs (50% survival for mutants compared to 7% survival for wild-type mice)
|
|
• mutants intratracheally infected with E.coli exhibit increased neutrophil recruitment to lungs and increased lung inflammation, pulmonary edema, and increased susceptibility to death compared to controls
|
|
• mutants exhibit an increase in pneumonia-associated death rate compared to wild-type mice, with only 50% of mutants surviving compared to 80% survival of wild-type mice
|
|
• macrophage recruitment to inflamed lungs is increased
|
|
• number of resident alveolar macrophages in unchallenged mutants is increased by more than 60% percent compared to wild-type
|
|
• neutrophils isolated from bone marrow live longer than wild-type neutrophils
(J:114699)
• neutrophils exhibit enhanced ruffling in response to the chemoattractant fMLP or IL-8
(J:145331)
• polarized neutrophils exhibit a considerable increase in multiple pseudopodia compared to wild-type mice
(J:145331)
• neutrophils show more diffuse F-actin localization at the leading edge or pseudopodia than wild-type neutrophils
(J:145331)
• fMLP-stimulated, but not PMA-stimulated, neutrophils exhibit increased and prolonged superoxide production compared to wild-type neutrophils
(J:145331)
• neutrophils exhibit enhanced transwell chemotaxis toward fMLP, IL-8 or C5a
(J:145331)
• neutrophils are more active and move faster than wild-type neutrophils but lack some of the directionality of wild-type neutrophils
(J:145331)
• in a model of peritonitis, neutrophil recruitment at sites of inflammation is increased in mutants compared to wild-type mice
(J:145331)
• in a model of bacterial pneumonia, apoptosis of lung recruited neutrophils is reduced in mutants compared to wild-type mice
(J:148947)
• neutrophils exhibit enhanced bacteria-killing capacity in a model of bacterial pneumonia
(J:148947)
• neutrophils have an increased phagocytic index compared to wild-type in a model of bacterial pneumonia
(J:148947)
• neutrophils exhibit enhanced E.coli and zymosan-induced phagocytosis-associated superoxide production
(J:148947)
|
|
• in a bacterial pneumonia model in which mutants are intratracheally infected with E.coli to induce lung inflammation, mutants exhibit an increase in bacteria-induced neutrophil recruitment compared to controls
• mutants treated with the chemotherapeutic drug, cyclophosphamide, to induce neutropenia, exhibit fewer neutrophils in the lungs than untreated mutants, but more neutrophils than drug treated wild-type mice
|
|
• increased neutrophil recruitment to lungs leads to pulmonary edema formation and increased protein accumulation
|
|
• increase in cytokine/chemokine concentrations in inflamed lungs of E.coli infected mutants due to increased numbers of resident alveolar macrophages and not due to enhanced capability of macrophages to produce cytokines or chemokines
|
|
• mutants made neutropenic with the chemotherapeutic drug, cyclophosphamide, exhibit decreased mortality after E.coli challenge compared to wild-type mice due to enhanced neutrophil accumulation in the lungs (50% survival for mutants compared to 7% survival for wild-type mice)
|
|
• mutants exhibit an increase in pneumonia-associated death rate compared to wild-type mice, with only 50% of mutants surviving compared to 80% survival of wild-type mice
|
|
• number of resident alveolar macrophages in unchallenged mutants is increased by more than 60% percent compared to wild-type
|
|
• increased neutrophil recruitment to lungs leads to pulmonary edema formation and increased protein accumulation
|
|
• mutants develop more severe lung inflammation in response to bacterial pneumonia than controls
|
|
• macrophage recruitment to inflamed lungs is increased
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the maximum survival is 24 days
|
|
• lung weight is 10-fold higher than that in control mice at 3 weeks old
|
|
• lung weight is 10-fold higher than that in control mice at 3 weeks old
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• TPA-treated ears exhibit increased edema and inflammatory infiltration compared with similarly treated wild-type ears
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• despite reduced neutrophil numbers and recruitment, the number of monocytes, recruitment of macrophages during peritonitis and macrophage survival and cytokine production after Toll-like receptor stimulation are normal
|
|
• in the blood, spleen and bone marrow
|
|
• the number of Mac-1+Gr1+ granulocytes is decreased in the bone marrow as well as decreased 80% in peripheral blood and 86% in spleen compared to in wild-type mice
|
|
• the number of neutrophils is reduced by 80% compared to in wild-type mice due to increased apoptosis of neutrophils
• however, mice that do not exhibit proper cre-mediated deletion survive
|
|
• apoptosis of neutrophils is enhanced
• however, mice that do not exhibit proper cre-mediated deletion survive
|
|
• mice exhibit an 80% decrease in neutrophils recruited to peritoneal cells treated with thioglycollate to induce peritonitis compared to similarly treated wild-type mice
|
|
• in the blood, spleen and bone marrow
|
|
• the number of Mac-1+Gr1+ granulocytes is decreased in the bone marrow as well as decreased 80% in peripheral blood and 86% in spleen compared to in wild-type mice
|
|
• the number of neutrophils is reduced by 80% compared to in wild-type mice due to increased apoptosis of neutrophils
• however, mice that do not exhibit proper cre-mediated deletion survive
|
|
• apoptosis of neutrophils is enhanced
• however, mice that do not exhibit proper cre-mediated deletion survive
|
|
• mice exhibit an 80% decrease in neutrophils recruited to peritoneal cells treated with thioglycollate to induce peritonitis compared to similarly treated wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median life span is 170 days
• longer median life span than Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice (170 vs. 22 days)
|
|
• lung weight and histology are indistinguishable from littermate control mice at 3-week old, compare with lung weight is 10-fold higher in Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice
|
|
• lung weight and histology are indistinguishable from littermate control mice at 3-week old
• but eventually develop lung tumors at older age
|
|
• lung weight and histology are indistinguishable from littermate control mice at 3-week old
• but eventually develop lung tumors at older age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• longer life span than Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice (>100 days in some cases)
|
|
• lung weight is less than Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice but higher than in normal mice
|
|
• lung weight is less than Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice
|
|
• lung weight is less than Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice but higher than in normal mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increase in the number of apoptotic cells in the glomeruli
|
|
• mutants exhibit excretion of high molecular weight proteins in the urine
|
|
• mutants exhibit excretion of albumin in the urine
|
|
• females develop severe nephropathy at 4-6 months of age
|
|
• kidney hypertrophy
|
|
• increase in kidney weight due to glomerulomegaly
|
|
• nephrons exhibit coarsening and fusion of podocyte foot processes
|
|
• cell destruction in the glomeruli is indicated by the accumulation of electrolucent material in podocyte foot processes
|
|
• fusion of podocyte foot processes
|
|
• glomerular basement membrane thickening
|
|
• increase in glomerular cell number
|
|
• mesangial hypercellularity
|
|
• severe glomerular inflammation associated with increased renal macrophage infiltration
|
|
• mesangial matrix expansion
|
|
• glomerulomegaly; glomeruli are enlarged in focal regions within the kidneys
|
|
• mutants exhibit excretion of high molecular weight proteins in the urine
|
|
• mutants exhibit excretion of albumin in the urine
|
|
• peritoneal macrophages exhibit defective phagocytosis resulting in impaired apoptotic cell uptake and an accumulation of apoptotic cells
|
|
• peritoneal macrophages exhibit lower phagosome content and smaller filopodia than control macrophages
|
|
• mutants exhibit a marked deposition of IgG in the mesangial matrix
|
|
• mutants exhibit a marked deposition of IgM in the mesangial matrix
|
|
• apoptotic cells in mutants cannot reduce proinflammatory response as in controls, indicating enhanced proinflammatory macrophage activation within the kidney glomeruli
|
|
• mutants develop autoantibodies against nuclear proteins, ssDNA, and dsDNA
|
|
• severe glomerular inflammation associated with increased renal macrophage infiltration
|
|
• peritoneal macrophages exhibit defective phagocytosis resulting in impaired apoptotic cell uptake and an accumulation of apoptotic cells
|
|
• peritoneal macrophages exhibit lower phagosome content and smaller filopodia than control macrophages
|
|
• mutants exhibit a marked deposition of IgG in the mesangial matrix
|
|
• mutants exhibit a marked deposition of IgM in the mesangial matrix
|
|
• apoptotic cells in mutants cannot reduce proinflammatory response as in controls, indicating enhanced proinflammatory macrophage activation within the kidney glomeruli
|
|
• mesangial hypercellularity
|
|
• increase in the number of apoptotic cells in the glomeruli
|
|
• peritoneal macrophages exhibit defective phagocytosis resulting in impaired apoptotic cell uptake and an accumulation of apoptotic cells
|
|
• kidney hypertrophy
|
|
• increase in kidney weight due to glomerulomegaly
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| systemic lupus erythematosus | DOID:9074 |
OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420 |
J:168799 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in vitro, mutant bone marrow neutrophils show a ~50% reduction in fMLP-induced chemotaxis relative to wild-type neutrophils both at 1 and 10 uM fMLP
• mutant neutrophils show a significant reduction in fMLP-induced F-actin formation, with a slower rate of actin polymerization relative to wild-type neutrophils
• however, both PMA- and fMLP-stimulated mutant bone marrow neutrophils exhibit normal superoxide production relative to wild-type neutrophils
|
|
• 3 hrs after induction of peritonitis by sodium periodate injection, circulating leukocyte counts are not significantly increased, unlike in wild-type controls
|
|
• 3 hrs after induction of peritonitis, only a small increase in peripheral neutrophil counts is observed, unlike in wild-type controls where circulating neutrophil counts are increased by >3-fold
|
|
• 3 hrs after sodium periodate injection into the peritoneum, mutant mice exhibit a >50% reduction in neutrophil accumulation at the site of inflammation relative to wild-type controls
|
|
• 3 hrs after i.p. injection of sodium periodate, mutant mice display impaired neutrophil chemotaxis and in vivo recruitment to sites of acute inflammation relative to wild-type controls
|
|
• in vitro, mutant bone marrow neutrophils show a ~50% reduction in fMLP-induced chemotaxis relative to wild-type neutrophils both at 1 and 10 uM fMLP
• mutant neutrophils show a significant reduction in fMLP-induced F-actin formation, with a slower rate of actin polymerization relative to wild-type neutrophils
• however, both PMA- and fMLP-stimulated mutant bone marrow neutrophils exhibit normal superoxide production relative to wild-type neutrophils
|
|
• 3 hrs after induction of peritonitis by sodium periodate injection, circulating leukocyte counts are not significantly increased, unlike in wild-type controls
|
|
• 3 hrs after induction of peritonitis, only a small increase in peripheral neutrophil counts is observed, unlike in wild-type controls where circulating neutrophil counts are increased by >3-fold
|
|
• 3 hrs after sodium periodate injection into the peritoneum, mutant mice exhibit a >50% reduction in neutrophil accumulation at the site of inflammation relative to wild-type controls
|
|
• in vitro, mutant bone marrow neutrophils show a ~50% reduction in fMLP-induced chemotaxis relative to wild-type neutrophils both at 1 and 10 uM fMLP
• mutant neutrophils show a significant reduction in fMLP-induced F-actin formation, with a slower rate of actin polymerization relative to wild-type neutrophils
• however, both PMA- and fMLP-stimulated mutant bone marrow neutrophils exhibit normal superoxide production relative to wild-type neutrophils
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decreased tissue factor pathway inhibitor protein activity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no differences in the morphological polarization, motility, or chemotactic efficiency of macrophages are seen in a complement C5a gradient chemotaxis assay
• macrophages exhibit normal Golgi morphology
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• change in actin cytoskeleton remodeling causing significant increase in percentage of Salmonella-infected cells and cells harbouring more than one bacterium per cell when bone marrow derived macrophages (BMDMs) were subjected to opsonized S. Typhimurium infection
• normal percentage of Salmonella-infected cells and cells harbouring more than one bacterium per cell when cytochalasin D pre-treated BMDMs were subjected to opsonized S. Typhimurium infection
|
|
• increased mobility in collagen matrix in vitro
|
|
• increased mobility in collagen matrix in vitro
|
|
• increased levels of CXCL2, CXCL10, CCL3, CCL4 and CCL5 after intravenous infection with Salmonella Typhimurium
|
|
• increased levels of CXCL10 after intravenous infection with Salmonella Typhimurium
|
|
• after intravenous infection with Salmonella Typhimurium
|
|
• after intravenous infection with Salmonella Typhimurium
|
|
• increased levels of TNFA after intravenous infection with Salmonella Typhimurium
|
|
• progressive increase in bacterial load, overall and in spleen and liver after intravenous or oral infection with Salmonella Typhimurium
• decreased survival rates after intravenous or oral infection with Salmonella Typhimurium
• higher bacterial load in lungs after infection with M. tuberculosis
• increased parenchymal infiltration by granulomatous reaction and lympho-histiocytic inflammatory cells in lungs after infection with M. tuberculosis
|
|
• increased levels of CXCL2, CXCL10, CCL3, CCL4 and CCL5 after intravenous infection with Salmonella Typhimurium
|
|
• increased levels of CXCL10 after intravenous infection with Salmonella Typhimurium
|
|
• after intravenous infection with Salmonella Typhimurium
|
|
• after intravenous infection with Salmonella Typhimurium
|
|
• increased levels of TNFA after intravenous infection with Salmonella Typhimurium
|
|
• progressive increase in bacterial load, overall and in spleen and liver after intravenous or oral infection with Salmonella Typhimurium
• decreased survival rates after intravenous or oral infection with Salmonella Typhimurium
• higher bacterial load in lungs after infection with M. tuberculosis
• increased parenchymal infiltration by granulomatous reaction and lympho-histiocytic inflammatory cells in lungs after infection with M. tuberculosis
|
|
• large parenchymal consolidation in lungs after infection with M. tuberculosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in vertebral cancellous bone at 12 weeks of age
|
|
• 17beta-estradiol has no effect on osteoclast apoptosis unlike in wild-type mice
|
|
• after ovariectomy mice lose cortical bone mass but not cancellous bone mass
|
|
• increase in the number of osteoclasts in vertebral cancellous bone at 12 weeks of age
• at 28 weeks of age, but not at 12 weeks, bone mass is reduced, trabecular width is decreased, and trabecular separation is increased in vertebral cancellous bone
|
|
• the number of osteoclast progenitors is increased 2 fold at 12 weeks of age
|
|
• in vertebral cancellous bone at 12 weeks of age
|
|
• 17beta-estradiol has no effect on osteoclast apoptosis unlike in wild-type mice
|
|
• in vertebral cancellous bone at 12 weeks of age
|
|
• 17beta-estradiol has no effect on osteoclast apoptosis unlike in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the lymph node
|
|
• in the spleen
|
|
• in the spleen
|
|
• in the lymph node
|
|
• in the spleen
|
|
• as in knock-out mice
|
|
• in the lymph node
|
|
• in the spleen
|
|
• in the spleen
|
|
• in the lymph node
|
|
• in the spleen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decrease in both Ly6Chi and Ly6low blood and bone marrow monocytes as compared to controls
|
|
• decrease in both Ly6Chi and Ly6low blood and bone marrow monocytes as compared to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• with prior treatment with glucocorticoid stress hormone followed by middle cerebral artery occlusion
|
|
• prior to glucocorticoid stress hormone treatments fail to exhibit a reduction in numbers of infiltrating monocytes in infarcted hemisphere unlike in wild-type mice
|
|
• with prior treatment with glucocorticoid stress hormone followed by middle cerebral artery occlusion
|
|
• prior treatment with glucocorticoid stress hormone fail to exhibit a reduction in numbers of infiltrating monocytes and IL6 protein levels in infarcted hemisphere after middle cerebral artery occlusion unlike in wild-type mice
|
|
• prior to glucocorticoid stress hormone treatments fail to exhibit a reduction in numbers of infiltrating monocytes in infarcted hemisphere unlike in wild-type mice
|
|
• in the ischemic cortex after middle cerebral artery occlusion
• in the hippocampus 12, but not 72, hours after kainic acid treatment
|
|
• prior treatment with glucocorticoid stress hormone fails to induce a decrease in IL6 levels in the ischemic cortex 24 h after middle cerebral artery occlusion
|
|
• with prior treatment with glucocorticoid stress hormone followed by middle cerebral artery occlusion
|
|
• prior treatment with glucocorticoid stress hormone fail to exhibit a reduction in numbers of infiltrating monocytes and IL6 protein levels in infarcted hemisphere after middle cerebral artery occlusion unlike in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decrease in Ly6low blood and bone marrow monocytes as compared to controls
|
|
• decrease in Ly6low blood and bone marrow monocytes as compared to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit an increase in colony-forming units in the blood
|
|
• 1.5-fold in the spleen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• acute myeloid leukemia in 4 of 10 mice
|
|
• all mice develop myeloproliferative disease with enhanced myeloid cell proliferation and differentiation
• 2 of 10 mice develop accelerated myeloproliferative disease
|
|
• all mice develop myeloproliferative disease with enhanced myeloid cell proliferation and differentiation
• 2 of 10 mice develop accelerated myeloproliferative disease
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in mice fed a high salt diet
|
|
• mice fed a high salt diet exhibit increased chloride ion content and concentration in the skin compared with control mice
• however, plasma levels are normal
|
|
• mice fed a high salt diet fail to exhibit an increase in lymphatic capillary density unlike control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• macrophages exhibit decreased mitochondrial aerobic metabolism at basal levels and maximal reserve capacities compared with control cells
|
| N |
• mice exhibit normal myeloid, T lymphoid and B lymphoid lineages and cell cycle of lineage progenitors
|
| N |
• mice exhibit normal myeloid, T lymphoid and B lymphoid lineages and cell cycle of lineage progenitors
• macrophages exhibit normal growth and cell cycle
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the total macrophage and collagen lesion contents are increased
• the percentage (normalized for lesion size) of collagen in lesions is increased; however, the percentages of macrophages and smooth muscle cells in the lesions are similar
|
|
• total atherosclerotic lesion area and the proportion of advanced lesions are significantly increased compared to mutant mice expressing Lrp1
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• impaired ability to internalize targets coated with LRP ligands
• however, phagocytosis of apoptotic cells in serum free conditions is similar to controls
|
|
• impaired ability to internalize targets coated with LRP ligands
• however, phagocytosis of apoptotic cells in serum free conditions is similar to controls
|
|
• impaired ability to internalize targets coated with LRP ligands
• however, phagocytosis of apoptotic cells in serum free conditions is similar to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• significant decrease in the number of activated glial cells in ischemic tissue after transient middle cerebral artery occlusion
|
|
• significant decrease in the number of activated glial cells in ischemic tissue after transient middle cerebral artery occlusion
|
|
• significant reduction in the accumulation of nitrotyrosine in the ischemic tissue
• treatment with PLAT fails to restore nitrotyrosine accumulation unlike in mice null for Plat
|
|
• 24 hours after transient middle cerebral artery occlusion
|
|
• significant decrease in the number of activated glial cells in ischemic tissue after transient middle cerebral artery occlusion
|
|
• significant reduction in the accumulation of nitrotyrosine in the ischemic tissue
• treatment with PLAT fails to restore nitrotyrosine accumulation unlike in mice null for Plat
|
|
• 24 hours after transient middle cerebral artery occlusion
|
|
• significant decrease in the number of activated glial cells in ischemic tissue after transient middle cerebral artery occlusion
|
|
• significant decrease in the number of activated glial cells in ischemic tissue after transient middle cerebral artery occlusion
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice appear normal at weaning but fail to gain weight
|
|
• increase in levels of circulating neutrophils
|
|
• increase in levels of circulating lymphocytes
|
|
• increase in levels of circulating monocytes
|
|
• IgG deposition in the glomeruli of kidneys
|
|
• macrophages exhibit an acute elevation of proinflammatory cytokines IL-1beta, IL-6, and IP-10, but not IL-10, in response to ingesting dying cells that is not seen in control macrophages
• however, neither bone marrow-derived macrophages nor peritoneal exudate macrophages from 52 week old mice show any defects in the engulfment of dying cells in vitro indicating normal phagocytic capacity
|
|
• levels of CXCL1, CCL4 and CCL2 are increased in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• increase in levels of circulating neutrophils
|
|
• increase in levels of circulating lymphocytes
|
|
• increase in levels of circulating monocytes
|
|
• IgG deposition in the glomeruli of kidneys
|
|
• macrophages exhibit an acute elevation of proinflammatory cytokines IL-1beta, IL-6, and IP-10, but not IL-10, in response to ingesting dying cells that is not seen in control macrophages
• however, neither bone marrow-derived macrophages nor peritoneal exudate macrophages from 52 week old mice show any defects in the engulfment of dying cells in vitro indicating normal phagocytic capacity
|
|
• levels of CXCL1, CCL4 and CCL2 are increased in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• mice develop a systemic lupus erythematosus-like disease (SLE)
|
|
• increase in serum levels of a broad array of antibodies against autoantigens commonly associated with SLE
|
|
• kidneys from aged mice show endocapillary proliferative glomerulonephritis
|
|
• mice show indications of kidney damage and show increased functional markers of kidney injury
|
|
• IgG and complement C1q deposition in the glomeruli of kidneys
|
|
• kidneys from aged mice show endocapillary proliferative glomerulonephritis
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| systemic lupus erythematosus | DOID:9074 |
OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420 |
J:235399 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants die from vascular collapse, intravascular coagulation and organ ischemia after gram-negative bacterial infection
• wild-type mice are more susceptible to LPS-induced sepsis than mutants, showing 63% mortality from endotoxemia compared to 17% mortality of mutants after 4 days
|
|
• macrophages isolated from mutants do not respond to ligands for TLR5 and TLR7
• less Il-6 or Il-12p40 in response to LPS or CpG olignucleotide stimulation, respectively, are secreted by mutant macrophages than by wild-type
• TNFalpha release is reduced in response to poly I:C stimulation compared to wild-type
|
|
• 7-week old mice produce less cytokines like Il-6, Il-12p40 and TNFalpha than wild-type mice after LPS treatment
|
|
• mutant show reduced response to LPS compared to wild-type
|
|
• 3 days following infection by Listeria monocytogenes, mutants show significant weight loss and reduction of serum IL-12p40 and also show higher bacterial burden than wild-type
• 60-90% of spleen white pulp follicles are destroyed after 3 days with severe loss of lymphocytes
• numerous necrotic foci and abscesses are observed in infected mutant livers
|
|
• macrophages isolated from mutants do not respond to ligands for TLR5 and TLR7
• less Il-6 or Il-12p40 in response to LPS or CpG olignucleotide stimulation, respectively, are secreted by mutant macrophages than by wild-type
• TNFalpha release is reduced in response to poly I:C stimulation compared to wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• macrophages exhibit decreased chemotaxis in response to HMGB1 compared with wild-type cells
• however, chemotaxis response to C5a is normal
|
|
• neutrophils exhibit impaired chemotaxis in response to HMGB1 compared with wild-type cells
• however, chemotaxis response to TNF-alpha is normal
|
|
• following intraperitoneal injection of HMGB1, neutrophil recruitment is decreased compared to in similarly treated wild-type mice
• however, recruitment following injection of TNF-alpha is normal
|
|
• macrophages exhibit decreased chemotaxis in response to HMGB1 compared with wild-type cells
• however, chemotaxis response to C5a is normal
|
|
• neutrophils exhibit impaired chemotaxis in response to HMGB1 compared with wild-type cells
• however, chemotaxis response to TNF-alpha is normal
|
|
• macrophages exhibit decreased chemotaxis in response to HMGB1 compared with wild-type cells
• however, chemotaxis response to C5a is normal
|
|
• neutrophils exhibit impaired chemotaxis in response to HMGB1 compared with wild-type cells
• however, chemotaxis response to TNF-alpha is normal
|
|
• following intraperitoneal injection of HMGB1, neutrophil recruitment is decreased compared to in similarly treated wild-type mice
• however, recruitment following injection of TNF-alpha is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• macrophages exhibit decreased chemotaxis in response to HMGB1 compared with wild-type cells
• however, chemotaxis response to C5a is normal
|
|
• neutrophils exhibit impaired chemotaxis in response to HMGB1 compared with wild-type cells
• however, chemotaxis response to TNF-alpha is normal
|
|
• following intraperitoneal injection of HMGB1, neutrophil recruitment is decreased compared to in similarly treated wild-type mice
• however, recruitment following injection of TNF-alpha is normal
|
|
• macrophages exhibit decreased chemotaxis in response to HMGB1 compared with wild-type cells
• however, chemotaxis response to C5a is normal
|
|
• neutrophils exhibit impaired chemotaxis in response to HMGB1 compared with wild-type cells
• however, chemotaxis response to TNF-alpha is normal
|
|
• macrophages exhibit decreased chemotaxis in response to HMGB1 compared with wild-type cells
• however, chemotaxis response to C5a is normal
|
|
• neutrophils exhibit impaired chemotaxis in response to HMGB1 compared with wild-type cells
• however, chemotaxis response to TNF-alpha is normal
|
|
• following intraperitoneal injection of HMGB1, neutrophil recruitment is decreased compared to in similarly treated wild-type mice
• however, recruitment following injection of TNF-alpha is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 50% survival at 6 months
|
|
• in some mice
|
|
• increased immature myeloid cell population in the bone marrow, spleen and liver
|
|
• in some mice
|
|
• acute myeloid leukemia after 12 months in some mice
• however, suppression of Prmt1 reduces leukemic cells
|
|
• in some mice
|
|
• in some mice
|
|
• increased immature myeloid cell population in the bone marrow, spleen and liver
|
|
• in some mice
|
|
• in some mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• past 4 months of age, mice display weight loss which is more severe than in mice heterozygous for both alleles
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal bone formation
|
|
• impaired
|
|
• impaired
|
|
• impaired
|
|
• impaired
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• DSS treated mice exhibit moderately reduced disease with reduced inflammation compared with control mice
|
|
• DSS treated mice exhibit moderately reduced disease with reduced inflammation compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increase in the number of apoptotic cells in the glomeruli
|
|
• mutants exhibit excretion of high molecular weight proteins in the urine
|
|
• mutants exhibit excretion of albumin in the urine
|
|
• females develop severe nephropathy at 4-6 months of age
|
|
• kidney hypertrophy
|
|
• increase in kidney weight due to glomerulomegaly
|
|
• nephrons exhibit coarsening and fusion of podocyte foot processes
|
|
• cell destruction in the glomeruli is indicated by the accumulation of electrolucent material in podocyte foot processes
|
|
• fusion of podocyte foot processes
|
|
• glomerular basement membrane thickening
|
|
• increase in glomerular cell number
|
|
• mesangial hypercellularity
|
|
• severe glomerular inflammation associated with increased renal macrophage infiltration
|
|
• mesangial matrix expansion
|
|
• glomerulomegaly; glomeruli are enlarged in focal regions within the kidneys
|
|
• mutants exhibit excretion of high molecular weight proteins in the urine
|
|
• mutants exhibit excretion of albumin in the urine
|
|
• peritoneal macrophages exhibit defective phagocytosis resulting in impaired apoptotic cell uptake and an accumulation of apoptotic cells
|
|
• peritoneal macrophages exhibit lower phagosome content and smaller filopodia than control macrophages
|
|
• mutants exhibit a marked deposition of IgG in the mesangial matrix
|
|
• mutants exhibit a marked deposition of IgM in the mesangial matrix
|
|
• apoptotic cells in mutants cannot reduce proinflammatory response as in controls, indicating enhanced proinflammatory macrophage activation within the kidney glomeruli
|
|
• mutants develop autoantibodies against nuclear proteins, ssDNA, and dsDNA
|
|
• severe glomerular inflammation associated with increased renal macrophage infiltration
|
|
• peritoneal macrophages exhibit defective phagocytosis resulting in impaired apoptotic cell uptake and an accumulation of apoptotic cells
|
|
• peritoneal macrophages exhibit lower phagosome content and smaller filopodia than control macrophages
|
|
• mutants exhibit a marked deposition of IgG in the mesangial matrix
|
|
• mutants exhibit a marked deposition of IgM in the mesangial matrix
|
|
• apoptotic cells in mutants cannot reduce proinflammatory response as in controls, indicating enhanced proinflammatory macrophage activation within the kidney glomeruli
|
|
• mesangial hypercellularity
|
|
• increase in the number of apoptotic cells in the glomeruli
|
|
• peritoneal macrophages exhibit defective phagocytosis resulting in impaired apoptotic cell uptake and an accumulation of apoptotic cells
|
|
• kidney hypertrophy
|
|
• increase in kidney weight due to glomerulomegaly
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| systemic lupus erythematosus | DOID:9074 |
OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420 |
J:168799 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• about half the number of NK cells in the spleen, lymph node, liver, and lung
• but no decrease is seen in the bone marrow
|
|
• decrease in numbers of memory phenotype CD8+ T cells, particularly in lymph nodes, spleen, and blood
|
|
• decrease in numbers of memory phenotype CD8+ T cells, particularly in lymph nodes, spleen, and blood
|
|
• decrease in the numbers of adoptively transferred transgenic CD8+ T cells compared to controls by 30 days after immunization
|
|
• about half the number of NK cells in the spleen, lymph node, liver, and lung
• but no decrease is seen in the bone marrow
|
|
• decrease in numbers of memory phenotype CD8+ T cells, particularly in lymph nodes, spleen, and blood
|
|
• decrease in numbers of memory phenotype CD8+ T cells, particularly in lymph nodes, spleen, and blood
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increase in immature CD11b+ CXCR3+ NK cells in spleen and bone marrow
• more mature KLRG-1+ CD11b+ NK cells are underrepresented in spleen and bone marrow
|
|
• about half the number of NK cells in the spleen, lymph node, liver, and lung
• but no decrease is seen in the bone marrow
|
|
• decrease in numbers of memory phenotype CD8+ T cells, particularly in lymph nodes, spleen, and blood
|
|
• decrease in numbers of memory phenotype CD8+ T cells, particularly in lymph nodes, spleen, and blood
|
|
• decrease in proliferation of CD27+ CD11b+ cells
• decrease in activation of adoptively transferred wild-type NK cells in response to lipopolysaccaride
|
|
• increase in immature CD11b+ CXCR3+ NK cells in spleen and bone marrow
• more mature KLRG-1+ CD11b+ NK cells are underrepresented in spleen and bone marrow
|
|
• about half the number of NK cells in the spleen, lymph node, liver, and lung
• but no decrease is seen in the bone marrow
|
|
• decrease in numbers of memory phenotype CD8+ T cells, particularly in lymph nodes, spleen, and blood
|
|
• decrease in numbers of memory phenotype CD8+ T cells, particularly in lymph nodes, spleen, and blood
|
|
• exaggerated contraction of adoptively transferred transgenic CD8+ T cells seen as early as 10 days after immunization
|
|
• decrease in proliferation of CD27+ CD11b+ cells
• decrease in activation of adoptively transferred wild-type NK cells in response to lipopolysaccaride
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• susceptibility to cold induced hypothermia at both 22C and 4C
|
|
• reduced about 65% when exposed to 4C
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice succumb to Schistosoma infection in ~54 days
|
|
• progressive weight loss begins 6 weeks after S. mansoni infection; some animals lose 20% of original body weight
|
|
• mice show a similar Th1 response to Il4ra-null mice and a Th2 response similar to wild-type in response to Schistosoma infection
|
|
• livers show impaired alternative macrophage activation compared to wild-type
|
|
• granulomas are similar to wild-type, but slightly larger and less compact: intestinal granulomas show massive inflammatory cell infiltration
|
|
• granulomas form
|
|
• mice develop protective immunity against Nippostrongylus brasiliensis, accompanied by Th2 development
|
|
• mice show 100% mortality during acute infection by Schistosoma mansoni; mean survival time is 54 days
|
|
• granulomas form
|
|
• level of fibrosis is similar to wild-type
|
|
• during infection by N. brasiliensis, mice develop goblet cell hyperplasis
|
|
• livers show impaired alternative macrophage activation compared to wild-type
|
|
• during infection by N. brasiliensis, mice develop goblet cell hyperplasis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in LPS-injected mice
|
|
• in LPS-injected mice compared with similarly treated wild-type mice
|
|
• in LPS-injected mice
|
|
• in LPS-injected mice
|
|
• in LPS-injected mice compared with similarly treated Il10ratm1.1Jack homozygotes
|
|
• in LPS-injected mice
|
|
• in LPS-injected mice
|
|
• in LPS-injected mice compared with similarly treated Il10ratm1.1Jack homozygotes
|
|
• LPS-injected mice exhibit increased CXCL10 and CXCL1 levels compared with similarly treated wild-type mice
|
|
• mice infected with T. muris exhibit increased cecum score compared with similarly treated wild-type mice
|
|
• in LPS-injected mice
|
|
• in LPS-injected mice compared with similarly treated wild-type mice
|
|
• in LPS-injected mice
|
|
• in LPS-injected mice
|
|
• in LPS-injected mice compared with similarly treated Il10ratm1.1Jack homozygotes
|
|
• in LPS-injected mice
|
|
• in LPS-injected mice
|
|
• in LPS-injected mice compared with similarly treated Il10ratm1.1Jack homozygotes
|
|
• LPS-injected mice exhibit increased CXCL10 and CXCL1 levels compared with similarly treated wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• one mouse exhibit rare leukemia with acute promyelocytic leukemia features
|
| N |
• hematopoietic stem cells exhibit normal ex vivo self-renewal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• increased number of Iba1-labeled activated microglia in the hippocampal CA1 and dentate gurus (DG) areas after intracerebroventricular (i.c.v.) LPS administration
|
|
|
• increased Il1b mRNA levels in the hippocampus after i.c.v. LPS administration
• increased IL-1beta protein levels in primary microglial cells after LPS administration for 24 h
|
|
|
• increased Tnf mRNA levels in the hippocampus after i.c.v. LPS administration
• increased TNF protein levels in primary microglial cells after LPS administration for 24 h
|
|
|
• increased mRNA expression of proinflammatory factors (Tnf, Il1b, Nos2 and Ptgs2) in the hippocampus after i.c.v. LPS administration
|
|
|
• increased number of Iba1-labeled activated microglia in the hippocampal CA1 and dentate gurus (DG) areas after intracerebroventricular (i.c.v.) LPS administration
|
|
|
• decreased number of NeuN-labeled intact neurons in the hippocampal CA1 and dentate gurus (DG) areas after i.c.v. LPS administration
|
|
|
• increased Nos2 (nitric oxide synthase 2, inducible; aka iNOS) and Ptgs2 (prostaglandin-endoperoxide synthase 2; aka cyclooxygenase-2, Cox2) mRNA levels in the hippocampus following i.c.v. LPS administration
|
|
N |
• no alterations in spontaneous locomotor activity (total moving distance) in the open field test 7 days after i.c.v. LPS administration at 2 months of age
|
|
|
• mice exhibit severe deficits in spatial memory formation after i.c.v. LPS administration
• in the Morris water maze test, the escape latency on training day 3, 4 and 5 is longer in LPS-treated mice relative to that in LPS-treated controls; in the probe test, LPS-treated mice show a reduced number of platform-site crossings, travel a shorter distance and spend less time in the target quadrant than LPS-treated controls
• in the Y-maze test, LPS-treated mice show a reduced number of alterations but no change in the total number of arm entries relative to LPS-treated controls
|
|
|
• increased number of Iba1-labeled activated microglia in the hippocampal CA1 and dentate gurus (DG) areas after intracerebroventricular (i.c.v.) LPS administration
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• differentiation and fusion of osteoclast progenitors is abnormal
|
|
• differentiation and fusion of osteoclast progenitors is abnormal
|
|
• differentiation and fusion of osteoclast progenitors is abnormal
|
|
• differentiation and fusion of osteoclast progenitors is abnormal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following cecal ligation and puncture, mice exhibit increased bacterial clearance compared with wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following L. monocytogenes infection
|
|
• following L. monocytogenes infection
|
|
• following L. monocytogenes infection, mice exhibit decreased circulating interferon-alpha and -beta and decreased bacterial numbers in the spleen and liver compared with wild-type mice
|
|
• following L. monocytogenes infection
|
|
• following L. monocytogenes infection
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in LPS-treated mice
|
|
• in LPS-treated mice
|
|
• in LPS-treated mice
|
|
• from LPS-treated bone marrow macrophages
|
|
• from LPS-treated bone marrow macrophages
|
|
• from LPS-treated bone marrow macrophages
|
|
• LPS-treated bone marrow macrophages exhibit increased TNF-alpha and IL6 but decreased IL10 production compared with similarly treated wild-type cells
• LPS-treated mice exhibit increased TNF-alpha, IL6, and IL10 serum levels compared with similarly treated wild-type mice
|
|
• in LPS-treated mice
|
|
• in LPS-treated mice
|
|
• in LPS-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• macrophages stimulated with macrophage colony-stimulating factor (M-CSF) in the presence of IL-6, but not IFN-gamma, show an increase in the inhibition of proliferation compared to controls, indicating that cells are hyperresponsive to IL-6 but not IFN-gamma
|
|
• macrophages stimulated with macrophage colony-stimulating factor (M-CSF) in the presence of IL-6, but not IFN-gamma, show an increase in the inhibition of proliferation compared to controls, indicating that cells are hyperresponsive to IL-6 but not IFN-gamma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• bone marrow cells exhibit normal reactive oxygen species levels
|
|
• with age
|
|
• older mice exhibit a reduction in mature cells and an increase in immature cells compared with control mice
|
|
• granulocyte-macrophage (GM), granulocyte-erythrocyte-macrophage-megakaryocyte (GEMM), and macrophage (M) colonies from splenocytes
|
|
• in older mice
|
|
• granulocyte-macrophage (GM), granulocyte-erythrocyte-macrophage-megakaryocyte (GEMM), and macrophage (M) colonies from splenocytes
|
|
• in older mice
|
|
• in older mice
|
|
• in the spleen of older mice
|
|
• in the spleen of older mice
|
|
• in the bone marrow of older mice
|
|
• in the spleen of older mice
|
|
• a 1.8-fold increase in LSK cells in young mice
• a 5.4-fold increase in LSK cells in young mice
• age-dependent increase in lineage-restricted progenitors
|
|
• splenic architecture becomes increasingly disorganized with age-dependent expansion of the spaces between lymphoid follicles
|
|
• mild in young mice
• overt in older mice
|
|
• bone marrow cells continue to grow in culture after control cells stop proliferating
|
|
• 10-fold increase in R-2-hydroxyglutarate
|
|
• in the spleen of older mice
|
|
• in the spleen of older mice
|
|
• in the bone marrow of older mice
|
|
• in the spleen of older mice
|
|
• splenic architecture becomes increasingly disorganized with age-dependent expansion of the spaces between lymphoid follicles
|
|
• mild in young mice
• overt in older mice
|
|
• mild in young mice
• overt in older mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• bone marrow cells exhibit normal reactive oxygen species levels and hematopoietic stem cell repopulation capacity
|
|
• with age
|
|
• older mice exhibit a reduction in mature cells and an increase in immature cells compared with control mice
|
|
• granulocyte-macrophage (GM), granulocyte-erythrocyte-macrophage-megakaryocyte (GEMM), and macrophage (M) colonies from splenocytes
|
|
• in older mice
|
|
• granulocyte-macrophage (GM), granulocyte-erythrocyte-macrophage-megakaryocyte (GEMM), and macrophage (M) colonies from splenocytes
|
|
• in older mice
|
|
• in older mice
|
|
• in the spleen of older mice
|
|
• in the spleen of older mice
|
|
• in the bone marrow of older mice
|
|
• in the spleen of older mice
|
|
• a 1.8-fold increase in LSK cells in young mice
• a 5.4-fold increase in LSK cells in young mice
• age-dependent increase in lineage-restricted progenitors
|
|
• splenic architecture becomes increasingly disorganized with age-dependent expansion of the spaces between lymphoid follicles
|
|
• mild in young mice
• overt in older mice
|
|
• bone marrow cells continue to grow in culture after control cells stop proliferating
|
|
• 10-fold increase in R-2-hydroxyglutarate
|
|
• in the spleen of older mice
|
|
• in the spleen of older mice
|
|
• in the bone marrow of older mice
|
|
• in the spleen of older mice
|
|
• splenic architecture becomes increasingly disorganized with age-dependent expansion of the spaces between lymphoid follicles
|
|
• mild in young mice
• overt in older mice
|
|
• mild in young mice
• overt in older mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following exposure to acid-induced acute lung injury
|
|
• following exposure to acid-induced acute lung injury
|
|
• following exposure to acid-induced acute lung injury, mice exhibit alleviated symptoms compared to wild-type mice with decreased changes in elastance and serum IL6 levels
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no alterations in bone density or osteoclast differentiation are observed due to a lack of cre expression in osteoclasts
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal production of TNF, IL-6, and other cytokines when stimulated with Pam2CSK4, LPS, or CpG DNA
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• a higher level of intimal cell (macrophage) apoptosis is observed in atherosclerotic lesions relative to controls after receiving a Western diet for 10 weeks
|
| N |
• after 4 weeks on a Western diet, mice have similar lesion areas in proximal aortas and no or very rarely detected macrophage apoptosis in the lesions, very similar to pathology observed in controls
|
|
• 8 week-old mice fed a Western diet for 4 weeks display proximal aorta lesions similar to control animals
• necrotic areas observed in lesions are larger than observed in controls after receiving a Western diet for 10 weeks
|
| N |
• mice show similar weights and levels of plasma lipoproteins to controls after 4 weeks on a Western diet
|
|
• a higher level of intimal cell (macrophage) apoptosis is observed in atherosclerotic lesions relative to controls after receiving a Western diet for 10 weeks
|
|
• a higher level of intimal cell (macrophage) apoptosis is observed in atherosclerotic lesions relative to controls after receiving a Western diet for 10 weeks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in mice infected with P. chabaudi
|
|
• in mice infected with P. chabaudi
|
|
• mice infected with P. chabaudi exhibit lower IL1b and TNF-alpha levels compared with control mice
• however, lethality is normal
|
|
• in mice infected with P. chabaudi
|
|
• in mice infected with P. chabaudi
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• peritoneal macrophages show increased susceptibility to apoptosis induced by free cholesterol loading and to oxidized LDL; increased susceptibility to UV irradiation and the phosphatase inhibitor staurosporine is also observed relative to controls
|
|
• peritoneal macrophages show increased susceptibility to apoptosis induced by free cholesterol loading and to oxidized LDL; increased susceptibility to UV irradiation and the phosphatase inhibitor staurosporine is also observed relative to controls
|
|
• peritoneal macrophages show increased susceptibility to apoptosis induced by free cholesterol loading and to oxidized LDL; increased susceptibility to UV irradiation and the phosphatase inhibitor staurosporine is also observed relative to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in LPS-treated mice
|
|
• 2-fold higher 3 hours after LPS treatment
|
|
• in LPS-treated mice
|
|
• 1.5-fold 1.5 hours after LPS treatment
|
|
• from bone marrow-derived macrophages stimulated with LPS at 3 and 12 hours
• from thioglycollate-elicited peritoneal neutrophils stimulated with LPS at 0, 6 and 12 hours
|
|
• from bone marrow-derived macrophages stimulated with LPS
|
|
• from thioglycollate-elicited peritoneal neutrophils stimulated with LPS at 6 hours
|
|
• from bone marrow-derived macrophages stimulated with LPS at 3 and 6 hours
• from thioglycollate-elicited peritoneal neutrophils stimulated with LPS at 0, 6 and 12 hours
|
|
• from bone marrow-derived macrophages stimulated with LPS only at 3 hours
• from thioglycollate-elicited peritoneal neutrophils stimulated with LPS at 0, 6 and 12 hours
|
|
• hyperinflammatory phenotype in bone marrow-derived macrophages stimulated with LPS
|
|
• LPS-treated mice exhibit increase mortality to endotoxemia and cytokine production compared with control mice
|
|
• 2-fold higher 3 hours after LPS treatment
|
|
• in LPS-treated mice
|
|
• 1.5-fold 1.5 hours after LPS treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• iron homeostasis is normal in these mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• defect in autophagy in nutrient starved macrophages
|
|
• defect in autophagy in nutrient starved macrophages
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• microglia are only activated (deramified) in hippocampus region following IL1beta injection rather than throughout the brain parenchyma
|
|
• microglia are only activated (deramified) in hippocampus region following IL1beta injection rather than throughout the brain parenchyma
|
|
• intracerebroventricular IL1beta injection does not result in leukocyte infiltration to the brain parenchyma in contrast to wild-type controls
|
|
• microglia are only activated (deramified) in hippocampus region following IL1beta injection rather than throughout the brain parenchyma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice fed standard chow or a high-fat diet exhibit normal adiposity and lymphocyte numbers in white adipose tissue
|
| N |
• mice fed standard chow or a high-fat diet exhibit normal weight gain
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the large intestine
|
|
• splenic interferon-gamma producing CD4+ T cells are increased in mice treated with PMA and ionomycin
|
|
• in the large intestine
|
|
• CD4+ cells produce increased levels of interferon-gamma
|
|
• IL-12 production is enhanced compared to in wild-type mice
|
|
• as early as 5 to 6 weeks, mice exhibit thickened colon walls with reduced glands compared to wild-type mice and by 24 weeks all regions of the colon are affected
|
|
• in the large intestine
|
|
• splenic interferon-gamma producing CD4+ T cells are increased in mice treated with PMA and ionomycin
|
|
• in the large intestine
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• few mice exhibit inflammation characteristic of colitis and symptoms were less severe than in Stat3 null mice
|
|
• interferon-gamma production is less than in Stat 3 null mice
|
|
• unlike in wild-type mice, LPS fails to induce cytokine production
|
|
• few mice exhibit inflammation characteristic of colitis and symptoms were less severe than in Stat3 null mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• splenomegaly develops at about 5 weeks of age
|
|
• marginal zone B cells are depleted
|
|
• marginal zone macrophages are reorganized
|
|
• splenomegaly develops at about 5 weeks of age
|
|
• marginal zone B cells are depleted
|
|
• marginal zone macrophages are reorganized
|
|
• splenomegaly develops at about 5 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• fewer macrophages in induced tumor tissue
|
|
• fewer macrophages in induced tumor tissue
|
|
• reduced size of induced lung tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 6 hours after LPS injection, TNF, Il12 and Ifng levels are significantly higher than in controls, but less than in Il10tm1Cgn homozygotes
|
|
• after 3 subcutaneous injections of LPS, mice show an exaggerated inflammatory response similar to response of complete Il10-deficient mice
• 5 days after flank injection of CpG, mice develop moderate belt-shaped lesions similar to controls with no sign of necrosis or granulocyte infiltration
|
|
• 6/10 animals died by 2 days post-LPS injection compared to 2/25 controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• upon TLR ligand stimulation, macrophages produce less TNF,Il-6 and Il-12p40 than those in conrols
|
|
• upon TLR ligand stimulation, macrophages produce less TNF,Il-6 and Il-12p40 than those in conrols
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice fed a high-fat diet exhibit worsened glucose intolerance and insulin sensitivity
|
|
• mice fed a high-fat diet exhibit worsened glucose intolerance and insulin sensitivity
|
| N |
• mice fed a high-fat diet exhibit normal diet-induced obesity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice were born at Mendelian frequencies and normal
• histopathologic examination of liver hematopoiesis was normal
• no increase of granulocyte progenitors was found in the born marrow
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• smaller mononuclear osteoclasts
|
|
• increased trabecular bone volume
• increased radiodensity
• irregular patterning of trabecular bone
|
|
• smaller mononuclear osteoclasts
|
|
• smaller mononuclear osteoclasts
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced survival rates after LPS injection or cecal ligation and puncture (CLP)
|
| N |
• normal M1/M2 macrophage polarization
• normal NFKB activation and TNFA, IL6 and IL1b production by macrophage colony-stimulating factor (M-CSF)-derived macrophages (MDMs) in response to Toll-like receptor (TLR) and Dectin1 ligands
• normal serum calcium, TNFA, IL6 and IL12 levels after LPS injection
• no intestinal inflammation
• normal TNFA, IL1b and IL17 expression in colon
|
|
• elevated serum IL1b levels after LPS injection
|
|
• increased immune cell infiltration in liver and kidney and, to a lower extent, brain and lung after LPS injection
• increased intestinal inflammation after oral DSS administration
|
|
• significantly decreased body weight at age 10-15 weeks
|
|
• more severe weight loss after oral DSS administration
|
| N |
• normal serum IGF1 level
|
|
• elevated serum IL1b levels after LPS injection
|
|
• increased vessel length and vascular hyperplasia at age P5
|
|
• vascular leakage in brain, lung, kidney and liver after LPS injection
• vascular leakage in intestines with or without oral DSS administration
|
|
• increased vessel length and vascular hyperplasia at age P5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• scattered foci of hepatic necrosis in LPS-treated mice
|
| N |
• mice do not become sick enough to require euthanasia unlike Zfp36tm1.2Xen homozygotes
|
|
• in some mice
• in LPS-treated mice
|
|
• modest at 3 to 4 months in female mice
|
|
• 110 fold in LPS-treated mice
|
|
• in some mice
|
|
• widespread inflammatory cell infiltrates in liver, kidney, and lung in LPS-treated mice
|
|
• LPS-treated mice exhibit dramatic signs of endotoxemia (lethargy, tachypnea, piloerection and decreased body temperature); elevated TNF serum levels; enlarged spleens and dilated small intestines, with widespread inflammatory cell infiltrates in liver, kidney, and lung; scattered foci of hepatic necrosis, glomerular hypercellularity, and pulmonary alveolitis; and 5-fold increase in serum alanine aminotransferase, a 2.2-fold increase in blood urea nitrogen, and a 3-fold increase in lactate dehydrogenase compared with control mice
|
|
• in LPS-treated mice
|
|
• mild inflammation and fibrosis in 3 of 4 mice at 8 months
|
|
• 2.2-fold in LPS-treated mice
|
|
• 110 fold in LPS-treated mice
|
|
• 5-fold in LPS-treated mice
|
|
• 3-fold in LPS-treated mice
|
|
• dramatic in LPS-treated mice
|
|
• dramatic in LPS-treated mice
|
|
• in LPS-treated mice
|
|
• mild inflammation and fibrosis in 3 of 4 mice at 8 months
|
|
• at 6.5 months in female mice
• at 9 months in male mice
|
|
• in some mice
• in LPS-treated mice
|
|
• modest at 3 to 4 months in female mice
|
|
• dilated in LPS-treated mice
|
|
• scattered foci of hepatic necrosis in LPS-treated mice
|
|
• in some mice
• in LPS-treated mice
|
|
• modest at 3 to 4 months in female mice
|
|
• glomerular hypercellularity in LPS-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice injected with UV-irradiated dying thymocytes into the spleen, liver, or kidney exhibit defective clearance of engulfed, dying cells and no induction of LC3-II, indicating failure of LC3-associated phagocytosis-dependent mechanism to degrade engulfed corpses
|
|
• serum CCL4 levels are increased in mice injected with UV-irradiated dying thymocytes
|
|
• serum IL-1beta levels are increased in mice injected with UV-irradiated dying thymocytes
|
|
• serum IL-10 levels are not increased in mutant mice injected with UV-irradiated dying thymocytes like in wild-type mice
|
|
• serum IL-6 levels are increased in mice injected with UV-irradiated dying thymocytes
|
|
• mice injected with UV-irradiated dying thymocytes into the spleen, liver, or kidney exhibit defective clearance of engulfed, dying cells and no induction of LC3-II, indicating failure of LC3-associated phagocytosis-dependent mechanism to degrade engulfed corpses
|
|
• serum CCL4 levels are increased in mice injected with UV-irradiated dying thymocytes
|
|
• serum IL-1beta levels are increased in mice injected with UV-irradiated dying thymocytes
|
|
• serum IL-10 levels are not increased in mutant mice injected with UV-irradiated dying thymocytes like in wild-type mice
|
|
• serum IL-6 levels are increased in mice injected with UV-irradiated dying thymocytes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no abnormalities are observed in cells of the myeloid lineage
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD4+ cells produce increased levels of interferon-gamma
|
|
• macrophages produce increased amounts of IL-12p40 that are comparable to in Stat3 null mice
|
|
• macrophages produce increased amounts of IL-6 that are comparable to in Stat3 null mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 7 days after skin wound injury
|
|
• 7 days after skin wound injury, mice exhibit reduced macrophage compared with control mice
• however, the rate of wound closure is normal
|
|
• 7 days after skin wound injury
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• production of oxygen reactive species is increased compared to when either gene product is absent
|
|
• sensitivity to hydrogen peroxide treatment is increased compared to when either gene product is absent
|
|
• in culture, macrophage cell death increases from 6.2% in wild-type cells and in Trsp null cells 31% to 53%
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die between 1 and 3 months
|
|
• in culture, macrophages exhibit a 1.6-fold increase in intracellular reactive oxygen species levels at day 3 and a 2-fold increase at day 5 compared to in wild-type cells
|
|
• in culture, macrophage cell death increases from 6.2% in wild-type cells to 31%
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• from tumors induced by DMBA
|
|
• from tumors induced by DMBA
|
|
• from tumors induced by DMBA
|
|
• from tumors induced by DMBA
|
|
• mice treated with 7,12-Dimethylbenz(a)anthracene/12-O-Tetradecanoylphorbol-13-acetate (DMBA) exhibit fewer tumors with a later onset compared with type mice
|
|
• mice treated with 7,12-Dimethylbenz(a)anthracene/12-O-Tetradecanoylphorbol-13-acetate (DMBA) exhibit fewer tumors with a later onset compared with type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal bone formation rate, mineral apposition rate and mineralizing surface
|
|
• enhanced osteoclastogenesis
• however, treatment with LiCl reverses enhanced osteoclastogenesis
|
|
• in trabecular bone
|
|
• reduced cortical periosteal and endosteal perimeter
|
|
• with reduced cortical major and minor diameter
|
|
• in LPS-treated mice
|
|
• enhanced osteoclastogenesis
• however, treatment with LiCl reverses enhanced osteoclastogenesis
|
|
• enhanced osteoclastogenesis
• however, treatment with LiCl reverses enhanced osteoclastogenesis
|
|
• enhanced osteoclastogenesis
• however, treatment with LiCl reverses enhanced osteoclastogenesis
|
|
• in LPS-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• femoral microarchitecture is normal at 1 and 4 months of age and bone marrow-derived macrophage cultures form a similar number of osteoclasts in vitro as controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• femoral microarchitecture is normal at 1 and 4 months of age and bone marrow-derived macrophage cultures form a similar number of osteoclasts in vitro as controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are runted prior to weaning
|
|
• mice exhibit lower body weights throughout life
• mice treated with an alpha IL-1R blocking antibody show weight gain
|
|
• sick mice exhibit enlarged spleen
|
|
• pronounced neutrophilia is seen in the duodenums, with neutrophilic infiltration of the submucosa and lamina propria that extends into the underlying muscularis externa
|
|
• sick mice exhibit enlarged spleen
|
|
• pronounced neutrophilia is seen in the joints, duodenums, and kidney glomeruli
• increase in neutrophils in the peripheral blood of sick mice compared to healthy littermates
• increase in levels of neutrophils in spleen, and in peripheral and mesenteric lymph nodes
• mice treated with an alpha IL-1R blocking antibody show decreased levels of neutrophils in both the spleen and lymph nodes
|
|
• slight increase of T cells in the spleen, however there are no changes in T cells in the lymph nodes
|
|
• decrease in blood lymphocytes
|
|
• B cell numbers are modestly decreased in the lymph nodes
|
|
• increase in monocytes in the peripheral blood of the sick mice compared to healthy littermates
• increase in levels of monocytes in spleen, and in peripheral and mesenteric lymph nodes
• mice treated with an alpha IL-1R blocking antibody show decreased levels of monocytes in both the spleen and lymph nodes
|
|
• serum levels of cytokines and chemokines (IL-1 alpha, IL-1 beta, IFN-gamma, IL-6, MCP-1) are elevated
• mice treated with an alpha IL-1R blocking antibody show decreased IL-1bbeta, MCP-1, and TNF levels, however, levels of IL-18 are unchanged
|
|
• mice develop severe limb swelling, most noticeably in the tibiotarsal (heel) joint
• tibiotarsal joint swelling is 100% penetrant, although age of onset varies, beginning as early as 4 weeks or as late as 10 weeks of age
• substantial neutrophilic infiltration with slight to severe bone and cartilage erosion is seen in the tibiotarsal joint
• mice treated with an alpha IL-1R blocking antibody show decreased tibiotarsal joint swelling
|
|
• sick mice exhibit enlarged spleen
|
|
• pronounced neutrophilia is seen in the joints, duodenums, and kidney glomeruli
• increase in neutrophils in the peripheral blood of sick mice compared to healthy littermates
• increase in levels of neutrophils in spleen, and in peripheral and mesenteric lymph nodes
• mice treated with an alpha IL-1R blocking antibody show decreased levels of neutrophils in both the spleen and lymph nodes
|
|
• slight increase of T cells in the spleen, however there are no changes in T cells in the lymph nodes
|
|
• decrease in blood lymphocytes
|
|
• B cell numbers are modestly decreased in the lymph nodes
|
|
• increase in monocytes in the peripheral blood of the sick mice compared to healthy littermates
• increase in levels of monocytes in spleen, and in peripheral and mesenteric lymph nodes
• mice treated with an alpha IL-1R blocking antibody show decreased levels of monocytes in both the spleen and lymph nodes
|
|
• serum levels of cytokines and chemokines (IL-1 alpha, IL-1 beta, IFN-gamma, IL-6, MCP-1) are elevated
• mice treated with an alpha IL-1R blocking antibody show decreased IL-1bbeta, MCP-1, and TNF levels, however, levels of IL-18 are unchanged
|
|
• sick mice exhibit enlarged lymph nodes
|
|
• mice exhibit systemic inflammation, with nearly all tissues showing neutrophilic infiltration
|
|
• pronounced neutrophilia is seen in the duodenums, with neutrophilic infiltration of the submucosa and lamina propria that extends into the underlying muscularis externa
|
|
• substantial neutrophilic infiltration with slight to severe bone and cartilage erosion is seen in the tibiotarsal joint
|
|
• mice show varying degrees of kidney damage, with some mice having fibrin and neutrophil accumulation within the glomeruli indicating necrotizing glomerulonephritis, while others have some glomeruli with only thickened membranes
|
|
• some mice exhibit glomeruli with only thickened membranes
|
|
• mice show varying degrees of kidney damage, with some mice having fibrin and neutrophil accumulation within the glomeruli indicating necrotizing glomerulonephritis, while others have some glomeruli with only thickened membranes
|
|
• mice develop severe limb swelling, most noticeably in the tibiotarsal (heel) joint
• tibiotarsal joint swelling is 100% penetrant, although age of onset varies, beginning as early as 4 weeks or as late as 10 weeks of age
• substantial neutrophilic infiltration with slight to severe bone and cartilage erosion is seen in the tibiotarsal joint
• mice treated with an alpha IL-1R blocking antibody show decreased tibiotarsal joint swelling
|
|
• substantial neutrophilic infiltration with slight to severe bone and cartilage erosion is seen in the tibiotarsal joint
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| primary immunodeficiency disease | DOID:612 |
OMIM:242850 OMIM:PS300755 |
J:260047 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in response to LPS treatment, mice exhibit increased lethality compared with control mice
|
| N |
• mice exhibit normal myelopoiesis
|
|
• in response to LPS treatment
|
|
• in response to LPS treatment
|
|
• in response to LPS treatment
|
|
• in response to LPS treatment
|
|
• in response to LPS treatment, mice exhibit increased lethality and increased serum levels of TNF, IL6, IL1B and IL12 compared with control mice
|
|
• in response to LPS treatment
|
|
• in response to LPS treatment
|
|
• in response to LPS treatment
|
|
• in response to LPS treatment
|
|
• in response to LPS treatment, mice exhibit increased lethality compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following C. albicans challenge, peritoneal macrophage exhibit reduced release of arachidonic acid and fail to produce TNF compared with wild-type cells
• however, macrophage exhibit normal arachidonic acid release in response to PMA and lipid metabolism
|
|
• of non-opsonized C. albicans
• no improvement with IL13 treatment
|
|
• in response to heat-killed C. albicans or non-opsonized zymosan
• however, response to LPS is normal
|
|
• following C. albicans challenge, macrophage exhibit reduced release of arachidonic acid, C. albicans phagocytosis, reactive oxygen species production (whether treated with IL13 and/or mannan or not) and yeast clearance compared with control cells
|
|
• following C. albicans challenge, peritoneal macrophage exhibit reduced release of arachidonic acid and fail to produce TNF compared with wild-type cells
• however, macrophage exhibit normal arachidonic acid release in response to PMA and lipid metabolism
|
|
• no improvement with IL13 treatment
• of non-opsonized C. albicans
|
|
• of non-opsonized C. albicans
• no improvement with IL13 treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in a zymosan induced peritonitis model, mice exhibit prolonged inflammation compared with control mice
• however, bone marrow-derived macrophage phagocytosis of zymosan is normal
|
|
• from bone marrow-derived macrophages in response to zymosan
|
|
• in a zymosan induced peritonitis model, mice exhibit prolonged inflammation compared with control mice
• however, bone marrow-derived macrophage phagocytosis of zymosan is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• high-fat diet fed mice exhibit reduced fasted and fed serum-free fatty acids
|
|
• mice fed a high-fat diet exhibit a minor increase in energy expenditure independent of any altered activity or respiratory quotient
|
|
• mice fed a high-fat diet exhibit increased glucose clearance after 16 weeks on the high-fat diet
|
|
• mice fed a high-fat diet exhibit increased insulin sensitivity after 16 weeks on the high-fat diet
|
|
• mice are resistance to high-fat diet induced metabolic disease
• however, mice fed a chow diet develop normally, exhibit normal white blood cell counts, and appear healthy, with no alterations in body weight, food intake, glucose tolerance, insulin sensitivity, or plasma-free fatty acid levels
|
|
• mice fed a high-fat diet exhibit a slightly reduced body weight gain compared to controls, despite similar food intake levels, although mice do become obese
|
|
• adipocyte size is reduced in epididymal fat from high-fat diet fed mice compared to controls on the same diet
|
|
• naive bone marrow derived macrophages from high-fat diet fed mice show elevated basal respiration and spare respiratory capacity
|
|
• naive bone marrow derived macrophages from high-fat diet fed mice show elevated basal and spare respiratory capacity and ATP-turnover
• increase in oxygen consumption rate of bone marrow derived macrophages from high-fat diet fed mice
|
|
• bone marrow derived macrophages from high-fat diet fed mice exhibit an increase in intracellular hydrogen peroxide and an increase of cytosolic reactive oxygen species
|
|
• IL-1 beta secretion by bone marrow derived macrophages from high-fat diet fed mice is reduced
|
|
• IL-6 secretion by bone marrow derived macrophages from high-fat diet fed mice is reduced
|
|
• TNF-alpha secretion by bone marrow derived macrophages from high-fat diet fed mice is reduced
|
|
• epididymal fat from high-fat diet fed mice shows improvements in metaflammation, with near absence of crown-like structures, reduced adipocyte size, and a reduction in macrophage infiltration
• adipose tissue from high-fat diet fed mice shows a 2-fold reduction in proinflammatory CD11c+ and CCR2+ macrophage infiltrates and an increase in numbers of protective M2-like MGL+ macrophages
|
|
• mice fed a high-fat diet exhibit attenuated liver steatosis compared to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal trabecular bone volume, trabecular bone mineral density, trabecular number, cortical thickness, cortical major and minor diameter, cortical periosteal and endosteal perimeter, and trabecular separation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• neutrophilic inflammation is not apparent
|
| N |
• mice exhibit normal joints
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal response by bone marrow-derived macrophages (BMDMs) to LPS, poly(I.C) and cGAMP
• normal percentage macrophages in peripheral blood
|
| N |
• normal percentage macrophages in peripheral blood
• normal response by bone marrow-derived macrophages (BMDMs) to LPS, poly(I.C) and cGAMP
|
|
• lack of interferon beta surge in BMDMs from MLV (murine leukemia virus) or HIV-infected mice
• normal interferon beta surge in bone marrow dendritic cells (BMDCs) from MLV (murine leukemia virus)-infected mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the serum of mice infected with VSV
|
|
• from macrophages infected with SeV or stimulated with 5'pppRNA
|
|
• mice infected with VSV exhibit reduced IFBN-beta serum levels, viral titers in the lung, liver, and spleen, inflammation, edema, and pulmonary fibrosis compared with wild-type mice
• however, response to HSV-1 infection is normal
|
|
• in the serum of mice infected with VSV
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal neutrophil and monocyte population as well as LPS-induced IL6 production
|
|
• in house-dust mite-exposed mice
• however, treatment with retinoic acid restores numbers
|
|
• in the lungs of house-dust mite-exposed mice
• however, treatment with retinoic acid restores numbers
|
|
• partially retarded development
|
|
• reduced CD11chigh and Siglec-Fhigh alveolar macrophages in bronchoalveolar lavage fluid and lungs
|
|
• house-dust mite-exposed mice exhibit exacerbated inflammation with increased IL4 and IL13, increased eosinophils, and decreased regulatory T cells in the lungs compared with wild-type mice
• however, the numbers of dendritic cells and interstitial macrophages are normal
|
|
• in the lung tissue of house-dust mite-exposed mice
|
|
• in the lung tissue of house-dust mite-exposed mice
|
|
• partially retarded development
|
|
• reduced CD11chigh and Siglec-Fhigh alveolar macrophages in bronchoalveolar lavage fluid and lungs
|
|
• reduced phagocytosis of ovalbumin protein
|
|
• in house-dust mite-exposed mice
• however, treatment with retinoic acid restores numbers
|
|
• in the lungs of house-dust mite-exposed mice
• however, treatment with retinoic acid restores numbers
|
|
• partially retarded development
|
|
• reduced CD11chigh and Siglec-Fhigh alveolar macrophages in bronchoalveolar lavage fluid and lungs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice fed a high-fat diet do not show differences in body weight or adiposity, or any improvements in glucose metabolism compared to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show increased susceptibility to DSS-induced colitis, showing increased weight loss, decrease in colon length, rapid mucosal damage with greater ulcer formations and frequent transmural inflammatory cell infiltrates consisting mostly of CD11b+ myeloid cells
• however, colons show comparable improvement with signs of intestinal epithelial cell regeneration and tissue repair as in wild-type mice
|
|
• mice show increased susceptibility to DSS-induced colitis, showing increased weight loss, decrease in colon length, rapid mucosal damage with greater ulcer formations and frequent transmural inflammatory cell infiltrates consisting mostly of CD11b+ myeloid cells
• however, colons show comparable improvement with signs of intestinal epithelial cell regeneration and tissue repair as in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show the presence of robust myeloid cell-driven systemic inflammation
|
| N |
• features of primary biliary cholangitis are not seen in mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice appear normal at weaning but fail to gain weight
|
|
• increase in levels of circulating neutrophils
|
|
• increase in levels of circulating lymphocytes
|
|
• increase in levels of circulating monocytes
|
|
• IgG deposition in the glomeruli of kidneys
|
|
• macrophages exhibit an acute elevation of proinflammatory cytokines IL-1beta, IL-6, and IP-10, but not IL-10, in response to ingesting dying cells that is not seen in control macrophages
• however, neither bone marrow-derived macrophages nor peritoneal exudate macrophages from 52 week old mice show any defects in the engulfment of dying cells in vitro indicating normal phagocytic capacity
|
|
• levels of CXCL1, CCL4 and CCL2 are increased in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• increase in levels of circulating neutrophils
|
|
• increase in levels of circulating lymphocytes
|
|
• increase in levels of circulating monocytes
|
|
• IgG deposition in the glomeruli of kidneys
|
|
• macrophages exhibit an acute elevation of proinflammatory cytokines IL-1beta, IL-6, and IP-10, but not IL-10, in response to ingesting dying cells that is not seen in control macrophages
• however, neither bone marrow-derived macrophages nor peritoneal exudate macrophages from 52 week old mice show any defects in the engulfment of dying cells in vitro indicating normal phagocytic capacity
|
|
• levels of CXCL1, CCL4 and CCL2 are increased in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• in 52-week old mice
|
|
• mice develop a systemic lupus erythematosus-like disease (SLE)
|
|
• increase in serum levels of a broad array of antibodies against autoantigens commonly associated with SLE
|
|
• kidneys from aged mice show endocapillary proliferative glomerulonephritis
|
|
• mice show indications of kidney damage and show increased functional markers of kidney injury
|
|
• IgG and complement C1q deposition in the glomeruli of kidneys
|
|
• kidneys from aged mice show endocapillary proliferative glomerulonephritis
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| systemic lupus erythematosus | DOID:9074 |
OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420 |
J:235399 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• round-shaped in vitro macrophage
|
|
• impaired formation of multinucleated giant-cell formation from peritoneal macrophages
|
|
• macrophages induce less T cell proliferation compared with control cells
• however, low spreading activity is normal
|
|
• reduced antigen presenting activity
|
|
• impaired formation of multinucleated giant-cell formation from peritoneal macrophages
|
|
• round-shaped in vitro macrophage
|
|
• impaired formation of multinucleated giant-cell formation from peritoneal macrophages
|
|
• macrophages induce less T cell proliferation compared with control cells
• however, low spreading activity is normal
|
|
• reduced antigen presenting activity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• macrophage exhibit induced tolerance to TLR4 and TLR9 ligands measured by hyporesponsiveness for the induction of TNF and IL6 after restimulation with LPS or CpG compared with control cells
|
|
• macrophage exhibit induced tolerance to TLR4 and TLR9 ligands measured by hyporesponsiveness for the induction of TNF and IL6 after restimulation with LPS or CpG compared with control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• injected tumors metastasize less efficiently than control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the number monocyte progenitors is not decreased; however, recombined progenitors can not differentiate into macrophages
• the ability of bone marrow progenitors to differentiate into granulocytes is not impaired
|
|
• the number monocyte progenitors is not decreased; however, recombined progenitors can not differentiate into macrophages
• the ability of bone marrow progenitors to differentiate into granulocytes is not impaired
|
|
• the number monocyte progenitors is not decreased; however, recombined progenitors can not differentiate into macrophages
• the ability of bone marrow progenitors to differentiate into granulocytes is not impaired
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• bone marrow-derived macrophages exhibit LPS-induced apoptosis unlike control cells
|
|
• bone marrow-derived macrophages exhibit LPS-induced apoptosis unlike control cells
|
|
• bone marrow-derived macrophages exhibit LPS-induced apoptosis unlike control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• TPA-treated ears exhibit reduced inflammatory infiltration and edema compared with similarly treated wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are normal until day 17 when they begin to die or must be euthanized
median survival is to day 20
|
|
• tumors range from atypical adenomatous hyperplasia, adenoma and adenocarcinoma at day 11 to diffuse adenocarsinoma that obliterate alveolar space by day 20
|
|
• at day 11
|
|
• beginning at day 11 and obliterating alveolar space by day 20
|
|
• lung weight increases 10-fold between day 18 and 22
|
|
• tumors range from atypical adenomatous hyperplasia, adenoma and adenocarcinoma at day 11 to diffuse adenocarsinoma that obliterate alveolar space by day 20
|
|
• at day 11
|
|
• beginning at day 11 and obliterating alveolar space by day 20
|
|
• after day 17
|
|
• percentage of neutrophil is higher in peripheral blood than in controls
|
|
• percentage of lymphocytes is lower than in controls
|
|
• pools of immature myeloid are present in the spleen
|
|
• pools of immature myeloid are present in the spleen
• myeloid proliferation is increased
|
|
• percentage of neutrophil is higher in peripheral blood than in controls
|
|
• percentage of lymphocytes is lower than in controls
|
|
• pools of immature myeloid are present in the spleen
|
|
• myeloid infiltration of the liver occurs
|
|
• after day 17
|
|
• lung weight increases 10-fold between day 18 and 22
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal LPS-induced mortality
|
| N |
• mice exhibit normal LPS-induced mortality
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die between 2 and 14 days after birth probably due to multisystem
organ failure secondary to inflammation and necrosis
• 70% of mice die between 7-14 days
• absence of B and T cells demonstrates disease is not caused by the adaptive immune system
|
|
• mutant pups gained weight slowly, and then lost weight before dying
|
|
• 1-2 day old mice have skin abscesses that develop into erythema and scaly skin by day 4
|
|
• 1-2 day old mice have skin abscesses that develop into erythema and scaly skin by day 4
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop chronic enterocolitis although it is not as severe as in Stat3 null mice
|
|
• splenic interferon-gamma producing CD4+ T cells are increased in mice treated with PMA and ionomycin but not a much as in Stat3 null mice
|
|
• intestinal lamina propria CD4+ T cells produce more interferon-gamma than wild-type cells
|
|
• macrophages produce more IL-6 than wild-type cells but less than Stat3 null cells
|
|
• macrophages produce more TNF-alpha than wild-type cells but less than Stat3 null cells
|
|
• as early as 5 to 6 weeks, mice exhibit thickened colon walls with reduced glands compared to wild-type mice but unlike in Stat3 null mice not all regions of the colon are affected
|
|
• mice develop chronic enterocolitis although it is not as severe as in Stat3 null mice
|
|
• splenic interferon-gamma producing CD4+ T cells are increased in mice treated with PMA and ionomycin but not a much as in Stat3 null mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die between 2 and 14 days after birth probably due to multisystem
organ failure secondary to inflammation and necrosis
• 70% of mice die between 7-14 days
|
|
• mutant pups gained weight slowly, and then lost weight before dying
|
|
• substantial necrosis occurs in the gut that is not associated with inflammation
|
|
• substantial necrosis occurs in the kidney that is not associated with inflammation
|
|
• white blood cell count is mildly elevated
|
|
• pronounced neutrophilia is evident in these mice
|
|
• GCSF is elevated in the sera of 6-8 day old mice
|
|
• CXCL1 levels are elevated in the sera of mice 6-8 days old
|
|
• IL-1beta levels in the sera of 6-8 day old mice are elevated 3-fold
• levels of this cytokine are also elevated in the dermis and epidermis, which may contribute to the skin pathology
|
|
• IL-18 levels are elevated in the sera of 6-8 day old mice
|
|
• IL-6 levels are elevated in the sera of 6-8 day old mice
• levels of this cytokine are also elevated in the dermis and epidermis, which may contribute to the skin pathology
|
|
• TNF levels in the sera of 6-8 day old mice are elevated
|
|
• mice have pronounced leukocytic infiltrates in skin, liver, spleen, joint, sinus, conjunctiva, bone marrow, and tongue that are mainly neutrophilic
|
|
• GCSF is elevated in the sera of 6-8 day old mice
|
|
• CXCL1 levels are elevated in the sera of mice 6-8 days old
|
|
• IL-1beta levels in the sera of 6-8 day old mice are elevated 3-fold
• levels of this cytokine are also elevated in the dermis and epidermis, which may contribute to the skin pathology
|
|
• IL-18 levels are elevated in the sera of 6-8 day old mice
|
|
• IL-6 levels are elevated in the sera of 6-8 day old mice
• levels of this cytokine are also elevated in the dermis and epidermis, which may contribute to the skin pathology
|
|
• TNF levels in the sera of 6-8 day old mice are elevated
|
|
• thrombocytosis is evident in these mice
|
|
• white blood cell count is mildly elevated
|
|
• pronounced neutrophilia is evident in these mice
|
|
• 1-2 day old mice have skin abscesses that develop into erythema and scaly skin by day 4
|
|
• 1-2 day old mice have skin abscesses that develop into erythema and scaly skin by day 4
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are either stillborn or day within one day of birth
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| familial cold autoinflammatory syndrome 1 | DOID:0090062 |
OMIM:120100 |
J:150054 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice survive longer than Pggt1btm1Mbrg Lyzstm1(cre)Ifo Krastm4Tyj heterozygotes with some surviving until day 98 when they were euthanized
|
|
• few, very mild adenomatous hyperplasia are present at day 11 and increase in occurence by day 62
• however, many segments of the lung are normal at day 62
|
|
• at day 98, progressed and scattered adenomas are present
|
|
• lung weight is less than in Pggt1btm1Mbrg Lyzstm1(cre)Ifo Krastm4Tyj heterozygotes but higher than in normal mice
|
|
• few, very mild adenomatous hyperplasia are present at day 11 and increase in occurence by day 62
• however, many segments of the lung are normal at day 62
|
|
• at day 98, progressed and scattered adenomas are present
|
|
• after day 40, mice grow slower than controls
• however, up to day 40 mice grow normally
|
|
• lung weight is less than in Pggt1btm1Mbrg Lyzstm1(cre)Ifo Krastm4Tyj heterozygotes but higher than in normal mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• during the early phase of skin wound healing, mice exhibit reduced amount, cellularity and vascularization of granulation tissue compared with control mice
• during the early to middle stage of wound healing, vascularization is increased compared to in control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• random motility (velocity and distance traveled) of macrophages plated on glass-bottomed dishes in presence of serum for 6 h
• macrophage phagocytosis for non-specific, CR3-mediated or Fc-receptor-mediated routes of entry
• adhesion in adherent macrophage cultures
|
|
• 47.8% decrease in number of macrophages forming podosomes
• 12.6% increase in cell surface area
|
|
• 38.6% reduction in F4/80 (Adgre1)-positive residential macrophages in liver
|
|
• 38.6% reduction in F4/80 (Adgre1)-positive residential macrophages (Kupffer cells) in liver
• 20% reduction in F4/80 (Adgre1)-positive macrophages in peritoneal cavity after thioglycollate-induced peritonitis
|
|
• increased amount of activated Rac1 (34.5%), Cdc42 (42.0%) and RhoA (59.4%) protein
|
|
• 50% reduction in migration in Transwell migration assay
|
|
• 47.8% decrease in number of macrophages forming podosomes
• 12.6% increase in cell surface area
|
|
• 38.6% reduction in F4/80 (Adgre1)-positive residential macrophages in liver
|
|
• 38.6% reduction in F4/80 (Adgre1)-positive residential macrophages (Kupffer cells) in liver
• 20% reduction in F4/80 (Adgre1)-positive macrophages in peritoneal cavity after thioglycollate-induced peritonitis
|
|
• increased amount of activated Rac1 (34.5%), Cdc42 (42.0%) and RhoA (59.4%) protein
|
|
• 50% reduction in migration in Transwell migration assay
|
|
• 50% reduction in migration in Transwell migration assay
|
| N |
• peripheral blood monocyte count
|
|
• 38.6% reduction in F4/80 (Adgre1)-positive residential macrophages in liver
|
| N |
• body weight, morphology
• tissue morphology of lung, liver, kidney, bone, skin, small intestine and large intestine
|
|
• 38.6% reduction in F4/80 (Adgre1)-positive residential macrophages in liver
|
| N |
• viable and survive to age 2 years without health abnormalities
|
| N |
• fecund
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced survival when challenged with lipopolysaccharide
|
|
• red blood cells in the bronchiolar and alveolar spaces of the lungs
|
|
• reduced ambulatory activity
|
|
• general increase in inflammatory cytokines
|
|
• enhanced infiltration of peritoneum
• increases in the spleen and circulation
• increased infiltration of the kidneys
• increased infiltration of bronchiolar and alveolar spaces of the lungs
|
|
• general increase in inflammatory cytokines
|
|
• enhanced infiltration of peritoneum
• increases in the spleen and circulation
• increased infiltration of the kidneys
• increased infiltration of bronchiolar and alveolar spaces of the lungs
|
|
• enhanced infiltration of peritoneum
• increases in the spleen and circulation
• increased infiltration of the kidneys
• increased infiltration of bronchiolar and alveolar spaces of the lungs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal acute-phase response to turpentine challenge
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice treated with AOM/DSS exhibit normal body weight loss, decreased colon length, inflammation and tissue damage
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduction in Tr1 (CD4+FOXP3-PD1hiIL10+) cells was observed at three weeks post H. pylori infection
|
|
• significant reduction in CX3CR1+ IL10-producing macrophages at three weeks post H. pylori infection
|
|
• reduction in Tr1 (CD4+FOXP3-PD1hiIL10+) cells was observed at three weeks post H. pylori infection
|
|
• significant reduction in CX3CR1+ IL10-producing macrophages at three weeks post H. pylori infection
|
|
• the gastric luminal burden of H. pylori was significantly decreased in a model of H. pylori infection
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/16/2024 MGI 6.23 |
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