Phenotypes associated with this allele

• Allele Symbol: Itgav^tm2.1Hyn
• Allele Name: targeted mutation 2.1, Richard Hynes
• Allele ID: MGI:3759837
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Itgav^tm2.1Hyn/Itgav^tm2.1Hyn	involves: 129P2/OlaHsd	MGI:5306157
cn2	Itgav^tm2Hyn/Itgav^tm2.1Hyn Cd19^tm1(cre)Cgn/Cd19^+	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * FVB	MGI:3759846
cn3	Itgav^tm2Hyn/Itgav^tm2.1Hyn Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * FVB	MGI:3759847
cn4	Itgav^tm2Hyn/Itgav^tm2.1Hyn Tg(Nes-cre)1Kln/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * FVB * SJL	MGI:5306156
cn5	Itgav^tm2Hyn/Itgav^tm2.1Hyn Tg(GFAP-cre)#Gtm/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:5306155
cn6	Itgav^tm2Hyn/Itgav^tm2.1Hyn Tg(Tek-cre)1Ywa/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:5306154
cn7	Itgav^tm2Hyn/Itgav^tm2.1Hyn Tg(Tek-cre)1Ywa/?	involves: 129S2/SvPas * C57BL/6 * FVB * SJL	MGI:3759849

Genotype
MGI:5306157

hm1

• Allelic Composition: Itgav^tm2.1Hyn/Itgav^tm2.1Hyn
• Genetic Background: involves: 129P2/OlaHsd

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

cardiovascular system

intracerebral hemorrhage ( J:94376 )

• severe

nervous system

intracerebral hemorrhage ( J:94376 )

• severe

Genotype
MGI:3759846

cn2

• Allelic Composition: Itgav^tm2Hyn/Itgav^tm2.1Hyn; Cd19^tm1(cre)Cgn/Cd19⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * FVB

digestive/alimentary system

digestive/alimentary phenotype ( J:125508 )

N • mice do not develop colitis unlike Itgav^tm2Hyn Itgav^tm2.1Hyn Tg(Tek-cre)1Ywa mice

Genotype
MGI:3759847

cn3

• Allelic Composition: Itgav^tm2Hyn/Itgav^tm2.1Hyn; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * FVB

immune system

impaired macrophage phagocytosis ( J:125508 )

• macrophages exhibit impaired ability to phagocytose and remove apoptotic cells

colitis ( J:125508 )

• mice develop colitis similar to Itgav^tm2Hyn/Itgav^tm2.1Hyn;Tg(Tek-cre)1Ywa mice with similar histology and proinflammatory cytokine expression but at a lower rate (30% compared to 100% of Itgav^tm2Hyn/Itgav^tm2.1Hyn;Tg(Tek-cre)1Ywa mice at 40 weeks)

increased autoantibody level ( J:125508 )

• mice contain higher levels of autoantibodies including ones against tropomyosin, phosphotidylserine, double-stranded DNA and anti-nuclear antibodies compared to in Itgav^tm2Hyn heterozygote controls

digestive/alimentary system

colitis ( J:125508 )

• mice develop colitis similar to Itgav^tm2Hyn/Itgav^tm2.1Hyn;Tg(Tek-cre)1Ywa mice with similar histology and proinflammatory cytokine expression but at a lower rate (30% compared to 100% of Itgav^tm2Hyn/Itgav^tm2.1Hyn;Tg(Tek-cre)1Ywa mice at 40 weeks)

hematopoietic system

impaired macrophage phagocytosis ( J:125508 )

• macrophages exhibit impaired ability to phagocytose and remove apoptotic cells

cellular

impaired macrophage phagocytosis ( J:125508 )

• macrophages exhibit impaired ability to phagocytose and remove apoptotic cells

Genotype
MGI:5306156

cn4

• Allelic Composition: Itgav^tm2Hyn/Itgav^tm2.1Hyn; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * FVB * SJL

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:94376 )

• mice have to be euthanized by 8 months due to urinary dysfunction and bacterial bladder infection

premature death ( J:94376 )

• some mice die by 4 weeks of age

• mice have to be euthanized by 8 months due to urinary dysfunction and bacterial bladder infection

nervous system

nervous system phenotype ( J:94376 )

N • mice do not exhibit peripheral nerve abnormalities

seizures ( J:94376 )

• more frequent by 6 months

convulsive seizures ( J:94376 )

abnormal brain vasculature morphology ( J:94376 )

• vascular abnormalities are initiated in the developing ganglionic eminences of the forebrain

• cerebral blood vessels are tortuous and distended compared to in control mice

intracranial hemorrhage ( J:94376 )

• microhemorrhage in the brain at 3 weeks

intracerebral hemorrhage ( J:94376 )

• 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

spinal hemorrhage ( J:94376 )

• microhemorrhage in the spinal cord at 3 weeks

abnormal glial cell morphology ( J:94376 )

• glial degeneration in the fasciculus gracilis white matter region

gliosis ( J:94376 )

abnormal embryonic/fetal subventricular zone morphology ( J:94376 )

• vascular abnormalities are initiated in the developing ganglionic eminences of the forebrain

axon degeneration ( J:94376 )

• in the fasciculus gracilis

axonal dystrophy ( J:94376 )

• in the fasciculus gracilis

demyelination ( J:94376 )

• in the spinal cord white matter

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:94376 )

• by 2 to 3 weeks, some mice develop motor dysfunction

• by 2 to 3 months, all mice exhibit hind limb coordination defects

abnormal involuntary movement ( J:94376 )

• mice exhibit involuntary tail wriggling

ataxia ( J:94376 )

impaired coordination ( J:94376 )

• on a rotarod

impaired limb coordination ( J:94376 )

• mice partially drag hind limbs

abnormal posture ( J:94376 )

• rigid at 2 to 3 months

abnormal gait ( J:94376 )

• rigid at 2 to 3 months

• mice exhibit toe-walking

• mice partially drag hind limbs

paraparesis ( J:94376 )

• spastic paraparesis by 6 months

seizures ( J:94376 )

• more frequent by 6 months

convulsive seizures ( J:94376 )

cardiovascular system

abnormal brain vasculature morphology ( J:94376 )

• vascular abnormalities are initiated in the developing ganglionic eminences of the forebrain

• cerebral blood vessels are tortuous and distended compared to in control mice

intracranial hemorrhage ( J:94376 )

• microhemorrhage in the brain at 3 weeks

intracerebral hemorrhage ( J:94376 )

• 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

spinal hemorrhage ( J:94376 )

• microhemorrhage in the spinal cord at 3 weeks

muscle

muscle phenotype ( J:94376 )

N • mice do not develop hind limb muscular atrophy

muscle hypertonia ( J:94376 )

• in hind limb muscles at 2 to 3 months

renal/urinary system

abnormal renal/urinary system physiology ( J:94376 )

• mice have to be euthanized by 8 months due to urinary dysfunction and bacterial bladder infection

immune system

increased susceptibility to bacterial infection induced morbidity/mortality ( J:94376 )

• mice have to be euthanized by 8 months due to urinary dysfunction and bacterial bladder infection

Genotype
MGI:5306155

cn5

• Allelic Composition: Itgav^tm2Hyn/Itgav^tm2.1Hyn; Tg(GFAP-cre)#Gtm/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

cardiovascular system

intracranial hemorrhage ( J:94376 )

• at E18 and P5, mice exhibit microhemorrhage in the cerebellum, mid-brain, and cerebral cortex unlike in control mice

cerebellum hemorrhage ( J:94376 )

• at E18 and P5, mice exhibit microhemorrhage in the cerebellum unlike in control mice

intracerebral hemorrhage ( J:94376 )

• 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

nervous system

intracranial hemorrhage ( J:94376 )

• at E18 and P5, mice exhibit microhemorrhage in the cerebellum, mid-brain, and cerebral cortex unlike in control mice

cerebellum hemorrhage ( J:94376 )

• at E18 and P5, mice exhibit microhemorrhage in the cerebellum unlike in control mice

intracerebral hemorrhage ( J:94376 )

• 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

Genotype
MGI:5306154

cn6

• Allelic Composition: Itgav^tm2Hyn/Itgav^tm2.1Hyn; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

cardiovascular system

cardiovascular system phenotype ( J:94376 )

N • mice exhibit normal cerebral vasculature

Genotype
MGI:3759849

cn7

• Allelic Composition: Itgav^tm2Hyn/Itgav^tm2.1Hyn; Tg(Tek-cre)1Ywa/?
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * FVB * SJL

mortality/aging

premature death ( J:125508 )

• median lifespan is reduced to 44 weeks compared to wild-type mice that live past 80 weeks

• mice die of intestinal constriction

immune system

abnormal immune system morphology ( J:125508 )

abnormal leukocyte morphology ( J:125508 )

abnormal dendritic cell differentiation ( J:125508 )

• 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

• CD11c^highCD103+ dendritic cells implicated in gut-homing are reduced in the mesenteric lymph nodes compared to in Itgav^tm2Hyn heterozygote controls

• however, bone marrow dendritic cells produce normal amount of regulatory T cells when cultured with CD4+CD25- T cells

decreased regulatory T cell number ( J:125508 )

• the number of regulatory T cells in the colon is decreased by 50% compared to in Itgav^tm2Hyn heterozygote controls and are predominantly adaptive regulatory T cells

increased regulatory T cell number ( J:125508 )

• the number of regulatory T cells in the spleen and mesenteric lymph nodes is increased compared to in Itgav^tm2Hyn heterozygote controls and are predominantly natural regulatory T cells

enlarged Peyer's patches ( J:125508 )

• Peyer's patches are enlarged and contain an increased proportion of activated CD4+ cells compared to control mice

enlarged mesenteric lymph nodes ( J:125508 )

• mesenteric lymph nodes are enlarged (15+/-1.1x10⁶ cells compared to 7.1+/-0.23 x10⁶ cells in Itgav^tm2Hyn heterozygote controls at 3 weeks ,and 34.2+/-6.7 x10⁶ cells compared to 8.6+/-1.6 x10⁶ cells in Itgav^tm2Hyn 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 Itgav^tm2Hyn heterozygote controls at week 3, and 31.7+/-0.40 x10⁶ cells compared to 15+/-0.81 x10⁶ cells in Itgav^tm2Hyn heterozygote controls at week 12)

abnormal immune system physiology ( J:125508 )

impaired macrophage phagocytosis ( J:125508 )

• 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

abnormal interferon level ( J:125508 )

• levels of interferon-gamma in serum and the intestine are elevated compared to in Itgav^tm2Hyn heterozygote controls

abnormal interleukin level ( J:125508 )

• IL-4 levels in serum and the intestine and IL-5 and IL-6 levels in the intestine are elevated compared to in Itgav^tm2Hyn heterozygote controls

• however, IL-12 and IL-23 levels in the intestine are normal

abnormal tumor necrosis factor level ( J:125508 )

• TNF-alpha levels in the intestine are elevated compared to in Itgav^tm2Hyn heterozygote controls

increased autoantibody level ( J:125508 )

• mice contain higher levels of autoantibodies including ones against tropomyosin, phosphotidylserine, double-stranded DNA and anti-nuclear antibodies compared to in Itgav^tm2Hyn heterozygote controls

increased inflammatory response ( J:125508 )

• mice develop inflammation in the peritoneum, in the liver, and 40% of mice nasal cavity and respiratory tract

large intestinal inflammation ( J:125508 )

• 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

colitis ( J:125508 )

digestive/alimentary system

abnormal intestinal epithelium morphology ( J:125508 )

• by 20 weeks of age, mice exhibit extensive epithelial proliferation and regeneration

crypts of Lieberkuhn abscesses ( J:125508 )

• by 20 weeks of age

intestinal ulcer ( J:125508 )

• by 20 weeks of age

increased intestinal adenocarcinoma incidence ( J:125508 )

• after 40 weeks of age

large intestinal inflammation ( J:125508 )

• 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

colitis ( J:125508 )

neoplasm

increased intestinal adenocarcinoma incidence ( J:125508 )

• after 40 weeks of age

growth/size/body

weight loss ( J:125508 )

• despite being born with normal weights and no developmental abnormalities, mice begin to lose weight and body condition at 12 weeks of age

hematopoietic system

impaired macrophage phagocytosis ( J:125508 )

• 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

abnormal leukocyte morphology ( J:125508 )

abnormal dendritic cell differentiation ( J:125508 )

• 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

• CD11c^highCD103+ dendritic cells implicated in gut-homing are reduced in the mesenteric lymph nodes compared to in Itgav^tm2Hyn heterozygote controls

• however, bone marrow dendritic cells produce normal amount of regulatory T cells when cultured with CD4+CD25- T cells

decreased regulatory T cell number ( J:125508 )

• the number of regulatory T cells in the colon is decreased by 50% compared to in Itgav^tm2Hyn heterozygote controls and are predominantly adaptive regulatory T cells

increased regulatory T cell number ( J:125508 )

• the number of regulatory T cells in the spleen and mesenteric lymph nodes is increased compared to in Itgav^tm2Hyn heterozygote controls and are predominantly natural regulatory T cells

endocrine/exocrine glands

crypts of Lieberkuhn abscesses ( J:125508 )

• by 20 weeks of age

homeostasis/metabolism

abnormal interferon level ( J:125508 )

• levels of interferon-gamma in serum and the intestine are elevated compared to in Itgav^tm2Hyn heterozygote controls

abnormal interleukin level ( J:125508 )

• IL-4 levels in serum and the intestine and IL-5 and IL-6 levels in the intestine are elevated compared to in Itgav^tm2Hyn heterozygote controls

• however, IL-12 and IL-23 levels in the intestine are normal

abnormal tumor necrosis factor level ( J:125508 )

• TNF-alpha levels in the intestine are elevated compared to in Itgav^tm2Hyn heterozygote controls

cellular

abnormal dendritic cell differentiation ( J:125508 )

• 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

• CD11c^highCD103+ dendritic cells implicated in gut-homing are reduced in the mesenteric lymph nodes compared to in Itgav^tm2Hyn heterozygote controls

• however, bone marrow dendritic cells produce normal amount of regulatory T cells when cultured with CD4+CD25- T cells

impaired macrophage phagocytosis ( J:125508 )

• 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