homeostasis/metabolism phenotype

• enhanced wound healing
  • days, tissues were normal in mutants but damage was maintained in wild-type
  (MGI Ref ID J:94497)
  • induction of colitis caused only 20% of mutant mice to develop serious diarrhea and to die within 48 hours compared to 100% of wild-type developing diarrhea and 50% dying
  (MGI Ref ID J:94497)
  • induction of colitis with rinitrobenzenesulfonic acid (TNBS) resulted in mucosal congestion, erosion, and hemorrhagic ulcerations of the distal colon and rectum in both wild-type and mutants, however the damage started to resolve after 72 hours and by 6-7 days, tissues were normal in mutants but damage was maintained in wild-type
  (MGI Ref ID J:94497)
  • induction of colitis resulted in reduced epithelial apoptosis in inflamed colon and faster resolution of colon damage compared to wild-type
  (MGI Ref ID J:94172)

• decreased susceptibility to injury
  • reduced plasma levels of nitrite/nitrate when colitis was induced
  (MGI Ref ID J:94172)

immune system phenotype

• decreased inflammatory response
  • neutrophil infiltration was prevented in TNBS treated mutant mice but not in wild-type
  (MGI Ref ID J:94497)

nervous system phenotype

• decreased neuron apoptosis
  • homozygotes are resistant to apoptosis typically induced by monocular deprivation in the dorsal lateral geniculate nucleus (dLGN)
  (MGI Ref ID J:65747)
  • in wild-type mice, monocular deprivation causes Trp53 accumulation, cell death, and progressive neuronal loss in the dLGN, with an early accumulation of citrulline
  (MGI Ref ID J:65747)

• decreased susceptibility to dopaminergic neuron neurotoxicity
  • homozygotes exhibit reduced susceptibility to damage induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
  (MGI Ref ID J:23942)

cellular phenotype

• decreased neuron apoptosis
  • in wild-type mice, monocular deprivation causes Trp53 accumulation, cell death, and progressive neuronal loss in the dLGN, with an early accumulation of citrulline
  (MGI Ref ID J:65747)
  • homozygotes are resistant to apoptosis typically induced by monocular deprivation in the dorsal lateral geniculate nucleus (dLGN)
  (MGI Ref ID J:65747)

• decreased cell proliferation
  • Normal - mutant mouse embryonic fibroblasts (MEFs) are able to efficiently repair DNA damaged by UV and alkylating agents
  (MGI Ref ID J:23942)
  • however, mutant MEFs exhibit a reduced proliferation rate relative to wild-type MEFs
  (MGI Ref ID J:23942)
  • in addition, mutant thymocyte progenitors show impaired proliferation and a slow recovery following whole-body gamma-radiation
  (MGI Ref ID J:23942)

• decreased susceptibility to dopaminergic neuron neurotoxicity
  • homozygotes exhibit reduced susceptibility to damage induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
  (MGI Ref ID J:23942)

homeostasis/metabolism phenotype

• decreased susceptibility to dopaminergic neuron neurotoxicity
  • homozygotes exhibit reduced susceptibility to damage induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
  (MGI Ref ID J:23942)

integument phenotype

• skin hyperplasia
  • older homozygotes are susceptible to spontaneous development of skin disease: ~30% of older mice develop epidermal hyperplasia
  (MGI Ref ID J:23942)
  • homozygotes are viable, fertile, of normal size, and do not display any gross physical or behavioral abnormalities
  (MGI Ref ID J:23942)

cellular phenotype

• decreased neuron apoptosis
  • wild-type neurons co-cultured with microglial cells exposed to TFN-alpha exhibit decreased cell death compared to neurons co-cultured with similarly treated wild-type microglial cells
  (MGI Ref ID J:96548)

• decreased renal tubule apoptosis
  • at 12 hrs post I/R injury, the number of apoptotic (TUNEL+) proximal tubule cells in the outer medulla is significantly decreased relative to that in similarly treated wild-type kidneys
  (MGI Ref ID J:95418)

immune system phenotype

• abnormal microglial cell physiology
  • LPS activation of microglial cells is suppressed compared with similarly treated wild-type cells
  (MGI Ref ID J:96548)
  • TNF-alpha fails to activate microglial cells unlike in similarly treated wild-type microglia
  (MGI Ref ID J:96548)

• decreased inflammatory response
  • following renal I/R injury, homozygotes exhibit decreased neutrophil infiltration (at 6, 12, and 24 hrs) and reduced expression of TNF-alpha, IL-1beta, and ICAM-1 (at 12 and 24 hrs) relative to similarly treated wild-type controls
  (MGI Ref ID J:95418)

nervous system phenotype

• abnormal microglial cell physiology
  • TNF-alpha fails to activate microglial cells unlike in similarly treated wild-type microglia
  (MGI Ref ID J:96548)
  • LPS activation of microglial cells is suppressed compared with similarly treated wild-type cells
  (MGI Ref ID J:96548)

• decreased neuron apoptosis
  • wild-type neurons co-cultured with microglial cells exposed to TFN-alpha exhibit decreased cell death compared to neurons co-cultured with similarly treated wild-type microglial cells
  (MGI Ref ID J:96548)

renal/urinary system phenotype

• decreased susceptibility to kidney reperfusion injury
  • Normal - however, no differences in the mortality rate, ROS levels, or number of nuclei with DNA strand breaks in proximal tubules are observed relative to wild-type controls
  (MGI Ref ID J:95418)
  • at 6, 12, and 24 hrs post I/R injury, kidney ATP levels are 80%, 73%, and 77%, respectively, of those in sham-operated controls, unlike in postischemic wild-type kidneys where ATP levels decline to 28%, 26%, and 43%
  (MGI Ref ID J:95418)
  • y 5) relative to similarly treated wild-type controls
  (MGI Ref ID J:95418)
  • following renal ischemic reperfusion (I/R) injury, homozygotes show significantly attenuated tubular cast formation, cellular necrosis, and red cell trapping in the corticomedullary region (day 1), and a significantly reduced number of dilated tubules (day 5) relative to similarly treated wild-type controls
  (MGI Ref ID J:95418)

• decreased renal tubule apoptosis
  • at 12 hrs post I/R injury, the number of apoptotic (TUNEL+) proximal tubule cells in the outer medulla is significantly decreased relative to that in similarly treated wild-type kidneys
  (MGI Ref ID J:95418)

• increased renal glomerular filtration rate
  • at 24 hrs post-renal I/R injury, GFR is significantly augmented relative to that in similarly treated wild-type controls
  (MGI Ref ID J:95418)

hematopoietic system phenotype

• abnormal microglial cell physiology
  • LPS activation of microglial cells is suppressed compared with similarly treated wild-type cells
  (MGI Ref ID J:96548)
  • TNF-alpha fails to activate microglial cells unlike in similarly treated wild-type microglia
  (MGI Ref ID J:96548)

homeostasis/metabolism phenotype

• decreased susceptibility to kidney reperfusion injury
  • at 6, 12, and 24 hrs post I/R injury, kidney ATP levels are 80%, 73%, and 77%, respectively, of those in sham-operated controls, unlike in postischemic wild-type kidneys where ATP levels decline to 28%, 26%, and 43%
  (MGI Ref ID J:95418)
  • following renal ischemic reperfusion (I/R) injury, homozygotes show significantly attenuated tubular cast formation, cellular necrosis, and red cell trapping in the corticomedullary region (day 1), and a significantly reduced number of dilated tubules (day 5) relative to similarly treated wild-type controls
  (MGI Ref ID J:95418)
  • Normal - however, no differences in the mortality rate, ROS levels, or number of nuclei with DNA strand breaks in proximal tubules are observed relative to wild-type controls
  (MGI Ref ID J:95418)
  • y 5) relative to similarly treated wild-type controls
  (MGI Ref ID J:95418)

• decreased physiological sensitivity to xenobiotic
  • LPS activation of microglial cells is suppressed compared with similarly treated wild-type cells
  (MGI Ref ID J:96548)

• abnormal response/metabolism to endogenous compounds
  • TNF-alpha fails to activate microglial cells unlike in similarly treated wild-type microglia
  (MGI Ref ID J:96548)

• decreased circulating creatinine level
  • at 1-3 days post-renal I/R injury, serum creatinine levels are significantly reduced relative to those in similarly treated wild-type controls
  (MGI Ref ID J:95418)

mammalian phenotype

• immune system phenotype
  • Normal - B cells exhibit no defect in IL4 rescue of cell death induced by death by neglect or after irradiation
  (MGI Ref ID J:146533)