Phenotypes Associated with This Genotype

Genotype
MGI:4942353

• Allelic Composition: Cd44^tm1Mak/Cd44^tm1Mak
• Genetic Background: B6.129P2-Cd44^tm1Mak

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

liver/biliary system

liver inflammation ( J:69351 )

• increased susceptibility to Concanavalin A (Con A)-induced hepatitis

• increased hepatocellular damage after Con A injection

• increased plasma aspartate aminotransferase levels, compared with WT mice

• similar active infiltration of mononuclear cells and neutrophils, compared with WT mice

• higher number of nuclei positive for DNA fragmentation in the liver compared with WT mice

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:69351 , J:111216 )

• all mice die within a few hours after Con A (20 mg/kg) injection, whereas WT mice survive (J:69351)

• more severe acute suppurative hepatitis after Con A (12 mg/kg) injection compared with WT mice (J:69351)

• increased mortality from lung injury (J:111216)

• 75% of mutant mice die by day 14, while wild-type mice survive but develop patchy lung fibrosis after bleomycin treatment (J:111216)

cellular

decreased sensitivity to induced cell death ( J:69351 )

• lower percentage of apoptotic liver-infiltrating mononuclear cells at 16 h after Con A administration, compared with cells from WT mice

decreased activation-induced cell death of T cells ( J:69351 )

• lower percentage of apoptotic T cells at 16 and 24 h after Con A administration, compared with WT mice

• lower percentage of apoptotic cells in T cells at 8, 16, and 24 h after cultured in vitro with Con A or immobilized anti-CD3 mAb plus IL-2, compared with cells from WT mice

abnormal leukocyte migration ( J:108245 )

• neutrophils migrated through Matrigel in response to chemoattractants faster and in greater numbers than wild-type neutrophils in vitro

impaired macrophage phagocytosis ( J:111216 )

• impaired ability of mutant macrophages to ingest apoptotic PMNs in vivo

• marked defect in clearance of exogenous apoptotic PMNs from BAL fluid compared to wild-type mice

• 13-fold increase in the number of apoptotic cells in the lung tissue of mutant mice compared to the wild type after bleomycin treatment

immune system

decreased activation-induced cell death of T cells ( J:69351 )

• lower percentage of apoptotic T cells at 16 and 24 h after Con A administration, compared with WT mice

• lower percentage of apoptotic cells in T cells at 8, 16, and 24 h after cultured in vitro with Con A or immobilized anti-CD3 mAb plus IL-2, compared with cells from WT mice

abnormal leukocyte migration ( J:108245 )

• neutrophils migrated through Matrigel in response to chemoattractants faster and in greater numbers than wild-type neutrophils in vitro

impaired macrophage phagocytosis ( J:111216 )

• impaired ability of mutant macrophages to ingest apoptotic PMNs in vivo

• marked defect in clearance of exogenous apoptotic PMNs from BAL fluid compared to wild-type mice

• 13-fold increase in the number of apoptotic cells in the lung tissue of mutant mice compared to the wild type after bleomycin treatment

impaired natural killer cell mediated cytotoxicity ( J:110889 )

• reduced IL-2-activated NK cytotoxicity against tumor cell lines

• impaired binding (conjugate formation) to target cells

• normal lymphocyte development and normal numbers of leukocyte subpopulations

• normal IL-2-activated NK cell differentiation and activation

abnormal circulating cytokine level ( J:69351 )

increased circulating interferon-gamma level ( J:69351 )

• increased production of IFN-gamma at 24 h after Con A administration, compared with WT mice

increased circulating interleukin-2 level ( J:69351 )

• increased production of IL-2 at 24 h after Con A administration, compared with WT mice

increased circulating tumor necrosis factor level ( J:69351 )

• increased production of TNF-alpha at 8 h after Con A administration, compared with WT mice

liver inflammation ( J:69351 )

• increased susceptibility to Concanavalin A (Con A)-induced hepatitis

• increased hepatocellular damage after Con A injection

• increased plasma aspartate aminotransferase levels, compared with WT mice

• similar active infiltration of mononuclear cells and neutrophils, compared with WT mice

• higher number of nuclei positive for DNA fragmentation in the liver compared with WT mice

lung inflammation ( J:108245 , J:111216 )

• more severe capillary disruption and more neutrophil accumulation in the lungs 6 hours after instillation of Escherichia coli, compared to wild-type mice (J:108245)

• greater edema formation during pneumonias induced by Escherichia coli (J:108245)

• normal circulating leukocyte counts (J:108245)

• normal clearance of instilled bacteria (J:108245)

• normal neutrophil apoptosis (J:108245)

• succumb to unremitting inflammation following noninfectious lung injury (J:111216)

• massive infiltration of inflammatory cells within alveolar interstitium until death by respiratory failure by day 14 after bleomycin treatment (J:111216)

• increased total cell numbers, polymorphonuclear leukocytes (PMNs), macrophages, and lymphocytes numbers in bronchoalveolar lavage (BAL) until death (J:111216)

• persisted hyaluronan (HA) accumulation and continue to rise until death within the interstitium intermixed with inflammatory cells (J:111216)

behavior/neurological

enhanced coordination ( J:80446 )

• improved motor function in spontaneous and forced motor performance (rotarod test)

cardiovascular system

decreased myocardial infarct size ( J:80446 )

• reduced ischemic infarct compared with that of wild-type mice following transient and permanent occlusion of the middle cerebral artery (MCAO)

• microglia and astrocytes are activated in a similar fashion

increased mean systemic arterial blood pressure ( J:80446 )

• increased mean arterial blood pressure, but in normal ranges compared with wild-type mice 30 min after reperfusion

• no difference in cerebral blood flow, heart rate, pH, blood oxygen and carbon dioxide between mutant and wild-type mice prior to and after transient MCAO

• no obvious difference in cardiovasculature and in particular the cerebral vasculature

homeostasis/metabolism

decreased myocardial infarct size ( J:80446 )

• reduced ischemic infarct compared with that of wild-type mice following transient and permanent occlusion of the middle cerebral artery (MCAO)

• microglia and astrocytes are activated in a similar fashion

abnormal circulating cytokine level ( J:69351 )

increased circulating interferon-gamma level ( J:69351 )

• increased production of IFN-gamma at 24 h after Con A administration, compared with WT mice

increased circulating interleukin-2 level ( J:69351 )

• increased production of IL-2 at 24 h after Con A administration, compared with WT mice

increased circulating tumor necrosis factor level ( J:69351 )

• increased production of TNF-alpha at 8 h after Con A administration, compared with WT mice

decreased transforming growth factor beta level ( J:111216 )

• much lower levels of active TGF-beta1 in BAL fluid relative to wild-type animals after bleomycin treatment

• similar total TGF-beta1 (latent + active) level

respiratory system

lung inflammation ( J:108245 , J:111216 )

• more severe capillary disruption and more neutrophil accumulation in the lungs 6 hours after instillation of Escherichia coli, compared to wild-type mice (J:108245)

• greater edema formation during pneumonias induced by Escherichia coli (J:108245)

• normal circulating leukocyte counts (J:108245)

• normal clearance of instilled bacteria (J:108245)

• normal neutrophil apoptosis (J:108245)

• succumb to unremitting inflammation following noninfectious lung injury (J:111216)

• massive infiltration of inflammatory cells within alveolar interstitium until death by respiratory failure by day 14 after bleomycin treatment (J:111216)

• increased total cell numbers, polymorphonuclear leukocytes (PMNs), macrophages, and lymphocytes numbers in bronchoalveolar lavage (BAL) until death (J:111216)

• persisted hyaluronan (HA) accumulation and continue to rise until death within the interstitium intermixed with inflammatory cells (J:111216)

hematopoietic system

decreased activation-induced cell death of T cells ( J:69351 )

• lower percentage of apoptotic T cells at 16 and 24 h after Con A administration, compared with WT mice

• lower percentage of apoptotic cells in T cells at 8, 16, and 24 h after cultured in vitro with Con A or immobilized anti-CD3 mAb plus IL-2, compared with cells from WT mice

abnormal leukocyte migration ( J:108245 )

• neutrophils migrated through Matrigel in response to chemoattractants faster and in greater numbers than wild-type neutrophils in vitro

impaired macrophage phagocytosis ( J:111216 )

• impaired ability of mutant macrophages to ingest apoptotic PMNs in vivo

• marked defect in clearance of exogenous apoptotic PMNs from BAL fluid compared to wild-type mice

• 13-fold increase in the number of apoptotic cells in the lung tissue of mutant mice compared to the wild type after bleomycin treatment

impaired natural killer cell mediated cytotoxicity ( J:110889 )

• reduced IL-2-activated NK cytotoxicity against tumor cell lines

• impaired binding (conjugate formation) to target cells

• normal lymphocyte development and normal numbers of leukocyte subpopulations

• normal IL-2-activated NK cell differentiation and activation