cardiovascular system
• severe
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nervous system
• severe
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Allele Symbol Allele Name Allele ID |
Itgavtm2.1Hyn targeted mutation 2.1, Richard Hynes MGI:3759837 |
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Summary |
7 genotypes
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• severe
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• severe
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice do not develop colitis unlike Itgavtm2Hyn Itgavtm2.1Hyn Tg(Tek-cre)1Ywa mice
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• macrophages exhibit impaired ability to phagocytose and remove apoptotic cells
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• 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)
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• mice contain higher levels of autoantibodies including ones against tropomyosin, phosphotidylserine, double-stranded DNA and anti-nuclear antibodies compared to in Itgavtm2Hyn heterozygote controls
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• 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)
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• macrophages exhibit impaired ability to phagocytose and remove apoptotic cells
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• macrophages exhibit impaired ability to phagocytose and remove apoptotic cells
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice have to be euthanized by 8 months due to urinary dysfunction and bacterial bladder infection
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• some mice die by 4 weeks of age
• mice have to be euthanized by 8 months due to urinary dysfunction and bacterial bladder infection
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N |
• mice do not exhibit peripheral nerve abnormalities
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• vascular abnormalities are initiated in the developing ganglionic eminences of the forebrain
• cerebral blood vessels are tortuous and distended compared to in control mice
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• microhemorrhage in the brain at 3 weeks
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• at E14.5, mice develop small bilateral cerebral hemorrhages that become progressively more severe throughout embryogenesis unlike control mice
• less severe than in null mice
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• microhemorrhage in the spinal cord at 3 weeks
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• glial degeneration in the fasciculus gracilis white matter region
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• vascular abnormalities are initiated in the developing ganglionic eminences of the forebrain
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• in the fasciculus gracilis
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• in the fasciculus gracilis
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• in the spinal cord white matter
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• by 2 to 3 weeks, some mice develop motor dysfunction
• by 2 to 3 months, all mice exhibit hind limb coordination defects
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• mice exhibit involuntary tail wriggling
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• on a rotarod
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• mice partially drag hind limbs
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• rigid at 2 to 3 months
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• rigid at 2 to 3 months
• mice exhibit toe-walking
• mice partially drag hind limbs
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• spastic paraparesis by 6 months
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• vascular abnormalities are initiated in the developing ganglionic eminences of the forebrain
• cerebral blood vessels are tortuous and distended compared to in control mice
|
• microhemorrhage in the brain at 3 weeks
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• at E14.5, mice develop small bilateral cerebral hemorrhages that become progressively more severe throughout embryogenesis unlike control mice
• less severe than in null mice
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• microhemorrhage in the spinal cord at 3 weeks
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N |
• mice do not develop hind limb muscular atrophy
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• in hind limb muscles at 2 to 3 months
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• mice have to be euthanized by 8 months due to urinary dysfunction and bacterial bladder infection
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• mice have to be euthanized by 8 months due to urinary dysfunction and bacterial bladder infection
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• at E18 and P5, mice exhibit microhemorrhage in the cerebellum, mid-brain, and cerebral cortex unlike in control mice
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• at E18 and P5, mice exhibit microhemorrhage in the cerebellum unlike in control mice
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• at E18 and P5, mice exhibit microhemorrhage in the cerebral cortex unlike in control mice
• between P7 and P14, mice exhibit progressive reduction in cerebral microhemorrhage
• however, adult mice exhibit no hemorrhage or edema in the brain
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• at E18 and P5, mice exhibit microhemorrhage in the cerebellum, mid-brain, and cerebral cortex unlike in control mice
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• at E18 and P5, mice exhibit microhemorrhage in the cerebellum unlike in control mice
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• at E18 and P5, mice exhibit microhemorrhage in the cerebral cortex unlike in control mice
• between P7 and P14, mice exhibit progressive reduction in cerebral microhemorrhage
• however, adult mice exhibit no hemorrhage or edema in the brain
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal cerebral vasculature
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• median lifespan is reduced to 44 weeks compared to wild-type mice that live past 80 weeks
• mice die of intestinal constriction
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• mesenteric lymph node dendritic cells cultured with CD4+CD25- T cells produce only 1% regulatory T cells compared to 4% to 5% by control dendritic cells
• CD11chighCD103+ dendritic cells implicated in gut-homing are reduced in the mesenteric lymph nodes compared to in Itgavtm2Hyn heterozygote controls
• however, bone marrow dendritic cells produce normal amount of regulatory T cells when cultured with CD4+CD25- T cells
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• the number of regulatory T cells in the colon is decreased by 50% compared to in Itgavtm2Hyn heterozygote controls and are predominantly adaptive regulatory T cells
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• the number of regulatory T cells in the spleen and mesenteric lymph nodes is increased compared to in Itgavtm2Hyn heterozygote controls and are predominantly natural regulatory T cells
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• Peyer's patches are enlarged and contain an increased proportion of activated CD4+ cells compared to control mice
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• mesenteric lymph nodes are enlarged (15+/-1.1x106 cells compared to 7.1+/-0.23 x106 cells in Itgavtm2Hyn heterozygote controls at 3 weeks ,and 34.2+/-6.7 x106 cells compared to 8.6+/-1.6 x106 cells in Itgavtm2Hyn heterozygote controls at 12 weeks) and contain an increased proportion of activated CD4+ cells (20+/-0.81 x106 cells compared to 11+/-1.3 x106 cells in Itgavtm2Hyn heterozygote controls at week 3, and 31.7+/-0.40 x106 cells compared to 15+/-0.81 x106 cells in Itgavtm2Hyn heterozygote controls at week 12)
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• macrophages exhibit impaired ability to phagocytose and remove apoptotic cells with twice as many uncleared apoptotic cells present in the intestine
• macrophages are no longer sensitive to the inhibitory effects of RGD peptide
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• levels of interferon-gamma in serum and the intestine are elevated compared to in Itgavtm2Hyn heterozygote controls
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• IL-4 levels in serum and the intestine and IL-5 and IL-6 levels in the intestine are elevated compared to in Itgavtm2Hyn heterozygote controls
• however, IL-12 and IL-23 levels in the intestine are normal
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• TNF-alpha levels in the intestine are elevated compared to in Itgavtm2Hyn heterozygote controls
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• mice contain higher levels of autoantibodies including ones against tropomyosin, phosphotidylserine, double-stranded DNA and anti-nuclear antibodies compared to in Itgavtm2Hyn heterozygote controls
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• mice develop inflammation in the peritoneum, in the liver, and 40% of mice nasal cavity and respiratory tract
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• after 14 weeks of age, mice exhibit inflammation in the colon and cecum with infiltration of lymphocytes, monocytes and plasma cells
• inflammation is chronic and progressive leading to ulcers, acute inflammatory infiltrate and crypt abscesses by week 20 with extensive epithelial proliferation, regeneration and adenocarcinoma from 40 weeks
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• by 20 weeks of age, mice exhibit extensive epithelial proliferation and regeneration
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• by 20 weeks of age
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• by 20 weeks of age
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• after 40 weeks of age
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• after 14 weeks of age, mice exhibit inflammation in the colon and cecum with infiltration of lymphocytes, monocytes and plasma cells
• inflammation is chronic and progressive leading to ulcers, acute inflammatory infiltrate and crypt abscesses by week 20 with extensive epithelial proliferation, regeneration and adenocarcinoma from 40 weeks
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• after 40 weeks of age
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• despite being born with normal weights and no developmental abnormalities, mice begin to lose weight and body condition at 12 weeks of age
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• macrophages exhibit impaired ability to phagocytose and remove apoptotic cells with twice as many uncleared apoptotic cells present in the intestine
• macrophages are no longer sensitive to the inhibitory effects of RGD peptide
|
• mesenteric lymph node dendritic cells cultured with CD4+CD25- T cells produce only 1% regulatory T cells compared to 4% to 5% by control dendritic cells
• CD11chighCD103+ dendritic cells implicated in gut-homing are reduced in the mesenteric lymph nodes compared to in Itgavtm2Hyn heterozygote controls
• however, bone marrow dendritic cells produce normal amount of regulatory T cells when cultured with CD4+CD25- T cells
|
• the number of regulatory T cells in the colon is decreased by 50% compared to in Itgavtm2Hyn heterozygote controls and are predominantly adaptive regulatory T cells
|
• the number of regulatory T cells in the spleen and mesenteric lymph nodes is increased compared to in Itgavtm2Hyn heterozygote controls and are predominantly natural regulatory T cells
|
• by 20 weeks of age
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• levels of interferon-gamma in serum and the intestine are elevated compared to in Itgavtm2Hyn heterozygote controls
|
• IL-4 levels in serum and the intestine and IL-5 and IL-6 levels in the intestine are elevated compared to in Itgavtm2Hyn heterozygote controls
• however, IL-12 and IL-23 levels in the intestine are normal
|
• TNF-alpha levels in the intestine are elevated compared to in Itgavtm2Hyn heterozygote controls
|
• mesenteric lymph node dendritic cells cultured with CD4+CD25- T cells produce only 1% regulatory T cells compared to 4% to 5% by control dendritic cells
• CD11chighCD103+ dendritic cells implicated in gut-homing are reduced in the mesenteric lymph nodes compared to in Itgavtm2Hyn heterozygote controls
• however, bone marrow dendritic cells produce normal amount of regulatory T cells when cultured with CD4+CD25- T cells
|
• macrophages exhibit impaired ability to phagocytose and remove apoptotic cells with twice as many uncleared apoptotic cells present in the intestine
• macrophages are no longer sensitive to the inhibitory effects of RGD peptide
|
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 08/02/2024 MGI 6.24 |
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