behavior/neurological phenotype

• abnormal spatial working memory
  • age-matched 16 month old mutant mice more quickly relearn and retain new platform location than wild-type mice is reversal trial of water T maze
  (MGI Ref ID J:224676)

• decreased anxiety-related response
  • 16 month old mutant mice make more total open arm entries than age-matched wild-type mice
  (MGI Ref ID J:224676)
  • 16 month old mutant mice make more contacts with novel objects in first minute of test than age-matched wild-type mice
  (MGI Ref ID J:224676)
  • 16 month old mutant mice spend more ambulatory time in the center of the field than age-matched wild-type mice
  (MGI Ref ID J:224676)

• enhanced spatial learning
  • age-matched 16 month old mutant mice more quickly relearn and retain new platform location than wild-type mice is reversal trial of water T maze
  (MGI Ref ID J:224676)

• enhanced contextual conditioning behavior
  • 16 month old mutant mice exhibit increased freezing time during initial testing and 24 hours later as compared to age-matched wild-type mice
  (MGI Ref ID J:224676)
  • 4 month old mutant mice exhibit increased freezing time during training, but not retention
  (MGI Ref ID J:224676)

growth/size/body region phenotype

• decreased fetal weight
  • significantly reduced fetal weight
  (MGI Ref ID J:150898)
  • reduced fetus/placenta ratio
  (MGI Ref ID J:150898)

hematopoietic system phenotype

• abnormal neutrophil morphology
  • neutrophils that accumulate at the site of a local Shwartman response are round instead of flattened as in wild-type mice
  (MGI Ref ID J:113463)

• decreased susceptibility to autoimmune hemolytic anemia
  • no protection is seen with pathogenic IgM or IgA self-antibodies
  (MGI Ref ID J:145432)
  • mice are resistant to hemolytic anemia induced by self-binding IgG2a antibodies
  (MGI Ref ID J:145432)

homeostasis/metabolism phenotype

• decreased cerebral infarction size
  • significantly reduced infarct volume but mortality unaffected
  (MGI Ref ID J:123658)

• abnormal blood homeostasis
  • mouse serum fails to support neutrophil adhesion unlike serum from wild-type mice
  (MGI Ref ID J:113463)

immune system phenotype

• decreased susceptibility to autoimmune hemolytic anemia
  • mice are resistant to hemolytic anemia induced by self-binding IgG2a antibodies
  (MGI Ref ID J:145432)
  • no protection is seen with pathogenic IgM or IgA self-antibodies
  (MGI Ref ID J:145432)

• abnormal neutrophil morphology
  • neutrophils that accumulate at the site of a local Shwartman response are round instead of flattened as in wild-type mice
  (MGI Ref ID J:113463)

• abnormal inflammatory response
  • following exposure to LPS then challenge with TNF at the same site to initiate a local Shwartman response, mice fail to exhibit hemorrhage and exhibit reduced fibrin deposition compared to the thrombohemorrhagic vasculitis observed in wild-type mice despite normal neutrophil accumulation
  (MGI Ref ID J:113463)
  • te normal neutrophil accumulation
  (MGI Ref ID J:113463)

• brain inflammation
  • reduced granulocyte infiltration of infarct sites
  (MGI Ref ID J:123658)

nervous system phenotype

• increased neuron number
  • mutant mice do not exhibit age-dependent neuron loss in the hippocampal CA3 region from P30 to 16 months
  (MGI Ref ID J:224676)
  • neuron numbers in CA1, V1 cortex and cerebellum are similar to wild-type
  (MGI Ref ID J:224676)

• decreased cerebral infarction size
  • significantly reduced infarct volume but mortality unaffected
  (MGI Ref ID J:123658)

• abnormal synaptic plasticity
  • synaptic plasticity is improved as compared to age matched 12 month old wild-type mice
  (MGI Ref ID J:224676)

• abnormal synaptic vesicle number
  • protective effects (to a lesser extent) against synapse loss are also observed in hippocampal DG and V1 regions, but not in the CA1 region, at 16 months of age
  (MGI Ref ID J:224676)
  • synaptic puncta density in the hippocampal CA3 region is higher in mutant males than in wild-type males at 4 months of age; density is similar to wild-type at P30
  (MGI Ref ID J:224676)

• enhanced long term potentiation
  • observed in 12 month old mice as compared to age-matched wild-type
  (MGI Ref ID J:224676)

• abnormal hippocampus CA3 region morphology
  • mutant mice do not exhibit age-dependent neuron loss in the hippocampal CA3 region from P30 to 16 months
  (MGI Ref ID J:224676)

• brain inflammation
  • reduced granulocyte infiltration of infarct sites
  (MGI Ref ID J:123658)

• abnormal dendritic spine morphology
  • increased dendritic spine density is observed in the hippocampal CA3 region of 16 month old mice as compared to wild-type
  (MGI Ref ID J:224676)

• enhanced paired-pulse facilitation
  • observed in 12 month old mice as compared to age-matched wild-type
  (MGI Ref ID J:224676)

reproductive system phenotype

• prolonged estrous cycle
  • 5.42 days vs 4.41 days in controls
  (MGI Ref ID J:150898)

• impaired embryo implantation
  • insignificantly but consistently reduced level of implantation at day 8
  (MGI Ref ID J:150898)

• abnormal female reproductive system physiology
  (MGI Ref ID J:150898)

embryo phenotype

• abnormal blastocyst morphology
  • blastocyst count at 4 days is consistently but insignificantly lower than in controls
  (MGI Ref ID J:150898)

• decreased placental labyrinth size
  • labyrinth area significantly reduced at day 15 of pregnancy
  (MGI Ref ID J:150898)

• decreased spongiotrophoblast size
  • significantly reduced spongioblast at day 15 of pregnancy
  (MGI Ref ID J:150898)

• small placenta
  • reduced placenta area at day 15 of pregnancy
  (MGI Ref ID J:150898)

homeostasis/metabolism phenotype

• decreased susceptibility to injury
  • following exposure to ethanol, mice do not develop microvesicular or macrovesicular steatosis of the liver and do not accumulate excessive trglycerides as in wild-type mice
  (MGI Ref ID J:128218)
  • following exposure to ethanol, mice exhibit a reduced increased in alanine aminotransferase compared to in similarly treated wild-type mice
  (MGI Ref ID J:128218)

• abnormal blood coagulation
  • thrombus formation considerably reduced
  (MGI Ref ID J:44715)

• decreased urine albumin level
  • albuminuria 1/50 control levels after 0.5ng dose of anti glomerular basement membrane antiserum and 1/13 of control levels after 1 ng of antiserum
  (MGI Ref ID J:44715)

immune system phenotype

• glomerulonephritis
  • reduced neutrophil infiltration of glomerulus relative to controls when injected with 0.5 mg but not with 1.0mg of anti-glomerular basement membrane antiserum
  (MGI Ref ID J:44715)

liver/biliary system phenotype

• decreased susceptibility to hepatic steatosis
  • following exposure to ethanol, mice do not develop microvesicular or macrovesicular steatosis of the liver as in wild-type mice
  (MGI Ref ID J:128218)

renal/urinary system phenotype

• glomerulonephritis
  • reduced neutrophil infiltration of glomerulus relative to controls when injected with 0.5 mg but not with 1.0mg of anti-glomerular basement membrane antiserum
  (MGI Ref ID J:44715)

• decreased urine albumin level
  • albuminuria 1/50 control levels after 0.5ng dose of anti glomerular basement membrane antiserum and 1/13 of control levels after 1 ng of antiserum
  (MGI Ref ID J:44715)

homeostasis/metabolism phenotype

• decreased circulating free fatty acids level
  • plasma free polyunsaturdated fatty acid (linoleic acid and arachidonic acid) levels are decreased at 14 months of age
  (MGI Ref ID J:214214)

vision/eye phenotype

• abnormal retinal horizontal cell morphology
  • density of horizontal cells is decreased
  (MGI Ref ID J:214214)

• abnormal c-wave shape
  • the amplitude of the c-wave is reduced at 12 months of age, but not at 8 weeks of age
  (MGI Ref ID J:214214)
  • Normal - however, no other component of the dc-ERG is different
  (MGI Ref ID J:214214)

• abnormal eye electrophysiology
  • 24 hours after infection with 500 CFU of S. aureus, mice show a transient loss of b-wave amplitude; this stabilizes at a level of 66% of baseline values, similar to what is seen in eyes of infected wild-type mice
  (MGI Ref ID J:136745)

• abnormal retinal rod bipolar cell morphology
  • the number of rod bipolar cells is decreased at 14 months of age
  (MGI Ref ID J:214214)

• decreased b-wave amplitude
  • ERG b-waves are decreased at 12 months of age but not at younger ages
  (MGI Ref ID J:214214)

immune system phenotype

• decreased susceptibility to Coronaviridae infection
  • Normal - however, SARS-CoV MA15-infected mice show similar levels of viral titers in the lung and ratio of peak expiratory flow as in controls
  (MGI Ref ID J:286325)
  • mice show partial protection from intranasal infection with the mouse-adapted SARS-CoV MA15 compared to wild-type controls, showing no significant weight loss, decreased airway resistance associated with airway debris and exhalation force indicating improved respiratory function, reduced lung pathology, reductions in inflammatory monocytes and neutrophils and increases in dendritic cells and alveolar macrophages in the lungs by day 4 postinfection, and reduction in cytokine and chemokine responses in the lungs
  (MGI Ref ID J:286325)
  • SARS-CoV MA15-infected mice exhibit more airspace inflammation at day 2 postinfection than controls but his is reversed later in infection
  (MGI Ref ID J:286325)

• increased susceptibility to bacterial infection
  • Normal - mice infected with 500 CFU of S. aureus, show higher numbers of bacterial SFU (intraocular growth) at 24 and 48 hours post-infection, levels are indistinguishable from infected wild-type by 72 hours
  (MGI Ref ID J:136745)

mammalian phenotype

• vision/eye phenotype
  • Normal - eyes infected with 500 CFU S. aureus show mild signs of inflammation at 24 and 48 hours but appear normal at 72 hours
  (MGI Ref ID J:136745)

nervous system phenotype

• abnormal retinal horizontal cell morphology
  • density of horizontal cells is decreased
  (MGI Ref ID J:214214)

• abnormal retinal rod bipolar cell morphology
  • the number of rod bipolar cells is decreased at 14 months of age
  (MGI Ref ID J:214214)

cardiovascular system phenotype

• decreased vascular permeability
  • upeon reperfusion of ischemic intestine (jejunum), permeability index (PI) of injured C3-deficient mice is reduced compared to control treated wild-type (PI of 2.25 vs 3.26 in controls)
  (MGI Ref ID J:78613)

homeostasis/metabolism phenotype

• decreased susceptibility to injury
  • neutrophil infiltration at the site of injury was reduced
  (MGI Ref ID J:120567)
  • mice are resistant to ischemia reperfusion-induced renal injury
  (MGI Ref ID J:120567)
  • serum urea nitrogen is reduced 31% to 55% compared to wild-type mice subjected to ischemia reperfusion
  (MGI Ref ID J:120567)

• abnormal tumor necrosis factor level
  • treatment with HuC3 restores levels of Tnfa production in mutants to wild-type levels
  (MGI Ref ID J:44240)
  • levels of Tnfa in peritoneal lavage fluids are reduced in C3-deficient mice compared to controls at 1 hour (158 mg/pl vs 400 mg/pl) and 3 hours (218 mg/pl vs 663 pg/ml) after CLP
  (MGI Ref ID J:44240)

• decreased circulating interleukin-6 level
  • Il-6 production after vitamin D3 stimulation is significantly reduced
  (MGI Ref ID J:166640)
  • reduced levels at 6 and 24 hours after 6 and 24 hours of reperfusion
  (MGI Ref ID J:152533)

• increased circulating bilirubin level
  • after 70% partial hepatectomy
  (MGI Ref ID J:152533)

• decreased circulating alanine transaminase level
  • levels lower during reperfusion after ischemia than in controls
  (MGI Ref ID J:152533)

• increased circulating alanine transaminase level
  • after 70% partial hepatectomy
  (MGI Ref ID J:152533)

• abnormal enzyme/coenzyme level
  • lower levels of myeloperoxidase in livers at 6 and 24 hours of reperfusion
  (MGI Ref ID J:152533)

• decreased circulating tumor necrosis factor level
  • reduced TNFalpha levels at 6 and 24 hours after 6 and 24 hours of reperfusion
  (MGI Ref ID J:152533)

immune system phenotype

• abnormal humoral immune response
  • when immunized with a 10-fold higher amount of bacteriophage, mice show a weak IgG response but response is still 10-fold lower than wild-type
  (MGI Ref ID J:64282)
  • in response to immunization with bacteriophage (phiX174), a T cell dependent antigen, C3-deficient mice mount a weak Ig M response but fail to switch to IgG
  (MGI Ref ID J:64282)

• abnormal immune system morphology
  (MGI Ref ID J:44240)

• abnormal mast cell physiology
  • mast cells from mutants 1 or 3 hours after CLP show reduced degranulation compared to wild-type (75% of wild-type cells vs <50% of C3-deficient cells)
  (MGI Ref ID J:44240)
  • treatment with HuC3 results in comparable levels of mast cell degranulation to wild-type
  (MGI Ref ID J:44240)

• decreased osteoclast cell number
  • bone marrow cells incubated with 1,25(OH)2 vitamin D3 produce fewer osteoclasts than do cells from controls
  (MGI Ref ID J:166640)

• increased susceptibility to bacterial infection
  • treatment with HuC3 restore neutrophil numbers and enhance bacterial clearance to wild-type levels
  (MGI Ref ID J:44240)
  • at 1 or 3 hours after CLP, cytocentrifuge preparations or peritoneal fluid from C3-deficient mice have reduced neutrophil counts and large numbers of bacteria, compared to wild-type which have few or no bacteria
  (MGI Ref ID J:44240)
  • increased mortality from GBS infection compared to controls is limited to the first 3 days after challenge
  (MGI Ref ID J:30152)
  • LD₅₀ dose: control 6.3 x 10⁴ vs. 1.3 x 10³ in C3-deficient mice)
  (MGI Ref ID J:30152)
  • mice challenged with group B Streptococci (GBS) infection become bacteremic within 3 days and die or clear bacteria and survive; C3-deficient mice challenged with GBS infection showed a decreased LD₅₀ dose compared to immunocompetent controls (LD₅₀ dose: control 6.3 x 10⁴ vs. 1.3 x 10³ in C3-deficient mice)
  (MGI Ref ID J:30152)
  • when pregnant dams are immunized with immune rabbit serum, pups are not protected against lethal challenge on day 2 of life (15/20 pups die within 48 hours)
  (MGI Ref ID J:30152)

• abnormal immune system physiology
  (MGI Ref ID J:44240)

• abnormal spleen germinal center morphology
  (MGI Ref ID J:64282)

• decreased neutrophil cell number
  • 1 hour after CLP, 50% of peritoneal cells are neutrophils and after 3 hours, 90% are neutrophils while in C3-deficient mice, after 1 hour only 1% and 45% after 3 hours are neutrophils
  (MGI Ref ID J:44240)

• abnormal tumor necrosis factor level
  • levels of Tnfa in peritoneal lavage fluids are reduced in C3-deficient mice compared to controls at 1 hour (158 mg/pl vs 400 mg/pl) and 3 hours (218 mg/pl vs 663 pg/ml) after CLP
  (MGI Ref ID J:44240)
  • treatment with HuC3 restores levels of Tnfa production in mutants to wild-type levels
  (MGI Ref ID J:44240)

• decreased circulating interleukin-6 level
  • Il-6 production after vitamin D3 stimulation is significantly reduced
  (MGI Ref ID J:166640)
  • reduced levels at 6 and 24 hours after 6 and 24 hours of reperfusion
  (MGI Ref ID J:152533)

• liver inflammation
  • patic sinusoids; wild-type animals that receive higher doses of GBS showed similar lesions
  (MGI Ref ID J:30152)
  • mild hepatitis is observed in a small number (1/11) of mice surviving systemic challenge with GBS doses of 10² to 10⁵ CFU upon necropsy 15 days post-challenge; there are aggregates of mononuclear or polymorphonuclear leukocytes in hepatic sinusoids; wild-type animals that receive higher doses of GBS showed similar lesions
  (MGI Ref ID J:30152)

• decreased spleen germinal center number
  • after immunization, wild-type mice develop germinal centers (GC) in ~half of splenic follicles while ~10% of splenic follicles in C3-deficient mice contain GCs
  (MGI Ref ID J:64282)

• increased susceptibility to bacterial infection induced morbidity/mortality
  • in mice infected with S. pneumoniae
  (MGI Ref ID J:205353)

• decreased mast cell number
  • after CLP less peritoneal mast cells can be recovered from Cr3-deficient mice compared to controls
  (MGI Ref ID J:44240)

• decreased circulating tumor necrosis factor level
  • reduced TNFalpha levels at 6 and 24 hours after 6 and 24 hours of reperfusion
  (MGI Ref ID J:152533)

• decreased spleen germinal center size
  • diameter of GCs are less than that observed in wild-type
  (MGI Ref ID J:64282)

• abnormal cell-mediated immunity
  • in an in vitro assay, opsonization with serum from C3-deficient mice and 1% immune rabbit serum only resulted in a 0.2 log10 reduction in GBS CFU compared to a 1.0 log10 reduction by normal mouse serum
  (MGI Ref ID J:30152)

cellular phenotype

• focal hepatic necrosis
  • after 70% partial hepatectomy
  (MGI Ref ID J:152533)

• decreased hepatocyte proliferation
  • impaired hepatocyte proliferation after 30 minutes of ischemia during 70% partial hepatectomy
  (MGI Ref ID J:152533)

digestive/alimentary phenotype

• abnormal intestine morphology
  • mice show less evidence of infarction compared to controls
  (MGI Ref ID J:78613)

liver/biliary system phenotype

• abnormal liver physiology
  (MGI Ref ID J:152533)

• abnormal liver morphology
  • histological evidence of injury after 6 and 24 hours of reperfusion following ischemia
  (MGI Ref ID J:152533)

• focal hepatic necrosis
  • after 70% partial hepatectomy
  (MGI Ref ID J:152533)

• decreased liver regeneration
  • impaired regenerative response after 70% hepatectomy
  (MGI Ref ID J:152533)
  • significant hepatic injury after 30 minutes of ischemia during 70% partial hepatectomy
  (MGI Ref ID J:152533)

• liver inflammation
  • mild hepatitis is observed in a small number (1/11) of mice surviving systemic challenge with GBS doses of 10² to 10⁵ CFU upon necropsy 15 days post-challenge; there are aggregates of mononuclear or polymorphonuclear leukocytes in hepatic sinusoids; wild-type animals that receive higher doses of GBS showed similar lesions
  (MGI Ref ID J:30152)
  • patic sinusoids; wild-type animals that receive higher doses of GBS showed similar lesions
  (MGI Ref ID J:30152)

• decreased hepatocyte proliferation
  • impaired hepatocyte proliferation after 30 minutes of ischemia during 70% partial hepatectomy
  (MGI Ref ID J:152533)

• hepatic steatosis
  • increased steatosis after 70% hepatectomy
  (MGI Ref ID J:152533)

mammalian phenotype

• immune system phenotype
  • Normal - B cells from deficient mice show normal proliferative effects in response to surface IgM crosslinking
  (MGI Ref ID J:64282)
  • secondary immune responses are similar in wild type and mutant mice, so helper T cell function is normal
  (MGI Ref ID J:64282)
  • Normal - secondary immune responses are similar in wild-type and mutant mice, so helper T cell function is normal
  (MGI Ref ID J:64282)

mortality/aging

• increased sensitivity to induced morbidity/mortality
  • reconstitution of mice with ip. injection of purified human C3 (HuC3) reduces mortality from 100% to 40% in the first 24 hours
  (MGI Ref ID J:44240)
  • caecal ligation and puncture (CLP) causes greater mortality in mutants than wild-type in the first 24 hours after CLP (100 vs 20% mortality)
  (MGI Ref ID J:44240)

• increased susceptibility to bacterial infection induced morbidity/mortality
  • in mice infected with S. pneumoniae
  (MGI Ref ID J:205353)

• abnormal induced morbidity/mortality
  • poor survival (20%) after 30 minutes of ischemia while 70% partial hepatectomy performed
  (MGI Ref ID J:152533)

nervous system phenotype

• abnormal peripheral nervous system regeneration
  • locomotor recovery from spinal cord injury occurs more rapidly than in controls
  (MGI Ref ID J:112353)
  • grossly normal at 7 days after injury compared to controls which show marked necrosis and vacuolation in controls at 21 days
  (MGI Ref ID J:112353)
  • slight improvement in tissue at 24 hours aftwr injury but considerably improved relative to controls by 72 hours
  (MGI Ref ID J:112353)

skeleton phenotype

• decreased osteoclast cell number
  • bone marrow cells incubated with 1,25(OH)2 vitamin D3 produce fewer osteoclasts than do cells from controls
  (MGI Ref ID J:166640)

hematopoietic system phenotype

• decreased mast cell number
  • after CLP less peritoneal mast cells can be recovered from Cr3-deficient mice compared to controls
  (MGI Ref ID J:44240)

• decreased spleen germinal center size
  • diameter of GCs are less than that observed in wild-type
  (MGI Ref ID J:64282)

• abnormal mast cell physiology
  • mast cells from mutants 1 or 3 hours after CLP show reduced degranulation compared to wild-type (75% of wild-type cells vs <50% of C3-deficient cells)
  (MGI Ref ID J:44240)
  • treatment with HuC3 results in comparable levels of mast cell degranulation to wild-type
  (MGI Ref ID J:44240)

• abnormal spleen germinal center morphology
  (MGI Ref ID J:64282)

• decreased spleen germinal center number
  • after immunization, wild-type mice develop germinal centers (GC) in ~half of splenic follicles while ~10% of splenic follicles in C3-deficient mice contain GCs
  (MGI Ref ID J:64282)

• decreased neutrophil cell number
  • 1 hour after CLP, 50% of peritoneal cells are neutrophils and after 3 hours, 90% are neutrophils while in C3-deficient mice, after 1 hour only 1% and 45% after 3 hours are neutrophils
  (MGI Ref ID J:44240)

• decreased osteoclast cell number
  • bone marrow cells incubated with 1,25(OH)2 vitamin D3 produce fewer osteoclasts than do cells from controls
  (MGI Ref ID J:166640)