cellular phenotype

• increased splenocyte proliferation
  • lack of stimulatory effect of ConA
  (MGI Ref ID J:30994)

integument phenotype

• abnormal skin condition
  • cutaneous granulomatous lesions at 8 weeks
  (MGI Ref ID J:30994)

limbs/digits/tail phenotype

• absent limbs
  • autoamputation of 2-3 extremities by 8 weeks of age
  (MGI Ref ID J:30994)

mortality/aging

• premature death
  • Background Sensitivity - occasional survival to 16 weeks on an NFS or C3H background for larger individuals
  (MGI Ref ID J:30994)
  • Background Sensitivity - life span about 8 weeks whereas on a C57BL/6 background survival is about 3 weeks
  (MGI Ref ID J:30994)

growth/size/body region phenotype

• decreased body weight
  • weigh about 66% of control weight
  (MGI Ref ID J:30994)

hematopoietic system phenotype

• increased IgM level
  • increased secretion by splenocytes in culture
  (MGI Ref ID J:30994)
  • serum levels elevated relative to controls
  (MGI Ref ID J:30994)

• increased splenocyte proliferation
  • lack of stimulatory effect of ConA
  (MGI Ref ID J:30994)

immune system phenotype

• increased IgM level
  • serum levels elevated relative to controls
  (MGI Ref ID J:30994)
  • increased secretion by splenocytes in culture
  (MGI Ref ID J:30994)

• increased splenocyte proliferation
  • lack of stimulatory effect of ConA
  (MGI Ref ID J:30994)

• increased autoantibody level
  (MGI Ref ID J:30994)

endocrine/exocrine gland phenotype

• thymus atrophy
  • the thymus of 2-3 week old mice appear normal but the thymus of older mice show significant atrophy
  (MGI Ref ID J:5999)

respiratory system phenotype

• lung inflammation
  • lung lesions present as pneumonia induced by crystals, lamellar bodies, giant cells, and macrophages
  (MGI Ref ID J:5999)
  • pneumonia affects the entire lung
  (MGI Ref ID J:5999)

• abnormal lung morphology
  • lesions are also seen in subpleural areas
  (MGI Ref ID J:5999)
  • ultrastructural analysis show alveolar macrophages contain crystals and iron-positive brown granules
  (MGI Ref ID J:5999)
  • lung lesions are seen in mutant mice as young as 7 days old with focal accumulations of alveolar macrophages
  (MGI Ref ID J:5999)

• respiratory distress
  • developed as mice approached 30 days of age
  (MGI Ref ID J:5999)

growth/size/body region phenotype

• decreased body size
  • runted compared with normal siblings by one week old
  (MGI Ref ID J:5999)

hematopoietic system phenotype

• thymus atrophy
  • the thymus of 2-3 week old mice appear normal but the thymus of older mice show significant atrophy
  (MGI Ref ID J:5999)

immune system phenotype

• lung inflammation
  • lung lesions present as pneumonia induced by crystals, lamellar bodies, giant cells, and macrophages
  (MGI Ref ID J:5999)
  • pneumonia affects the entire lung
  (MGI Ref ID J:5999)

• thymus atrophy
  • the thymus of 2-3 week old mice appear normal but the thymus of older mice show significant atrophy
  (MGI Ref ID J:5999)

integument phenotype

• skin lesions
  • focal dermal accumulations of macrophages frequently associated with hair bulbs
  (MGI Ref ID J:5999)

growth/size/body region phenotype

• decreased body weight
  • about half of controls
  (MGI Ref ID J:72655)

respiratory system phenotype

• abnormal pulmonary alveolar system morphology
  • intra alveolar hemorrhage around 3 weeks of age leading to death
  (MGI Ref ID J:72655)

hematopoietic system phenotype

• abnormal microglial cell morphology
  • F4/80+ microglial cells are reduced in number
  (MGI Ref ID J:72655)

immune system phenotype

• abnormal microglial cell morphology
  • F4/80+ microglial cells are reduced in number
  (MGI Ref ID J:72655)

mortality/aging

• postnatal lethality, complete penetrance
  • death at around 3 weeks of age involving intra alveolar hemorrhage
  (MGI Ref ID J:72655)

nervous system phenotype

• abnormal astrocyte morphology
  • GFAP+ astrocytes decreased about 50% on both the hippocampus and the forebrain fiber tracts
  (MGI Ref ID J:72655)

• abnormal CNS glial cell morphology
  (MGI Ref ID J:72655)

• abnormal forebrain morphology
  (MGI Ref ID J:72655)

• abnormal microglial cell morphology
  • F4/80+ microglial cells are reduced in number
  (MGI Ref ID J:72655)

• decreased brain size
  • length and width decreased
  (MGI Ref ID J:72655)
  • weight normal
  (MGI Ref ID J:72655)

• abnormal myelination
  • decreased
  (MGI Ref ID J:72655)

• abnormal hippocampus development
  • scattered areas of focal necrosis
  (MGI Ref ID J:72655)

• abnormal telencephalon development
  • scattered areas of focal necrosis in the cortex
  (MGI Ref ID J:72655)

• abnormal hippocampus CA1 region morphology
  • about 20% more neurons present
  (MGI Ref ID J:72655)

• abnormal nervous system morphology
  (MGI Ref ID J:72655)

immune system phenotype

• increased microglial cell activation
  • Normal - no difference from controls if ablation performed at 21 days of age
  (MGI Ref ID J:88807)
  • microglial cells seem transformed to the amoeboid activated state
  (MGI Ref ID J:88807)
  • level of activation is significantly higher at 4 days after operation but not at 2 or 6 days
  (MGI Ref ID J:88807)
  • significantly activated relative to controls as measured in the anteroventricular cochlear nucleus when unilateral cochlear ablation is performed at 14 days
  (MGI Ref ID J:88807)
  • no activation if cochlear ablation is performed at 5 days of age
  (MGI Ref ID J:88807)

nervous system phenotype

• increased microglial cell activation
  • microglial cells seem transformed to the amoeboid activated state
  (MGI Ref ID J:88807)
  • no activation if cochlear ablation is performed at 5 days of age
  (MGI Ref ID J:88807)
  • Normal - no difference from controls if ablation performed at 21 days of age
  (MGI Ref ID J:88807)
  • level of activation is significantly higher at 4 days after operation but not at 2 or 6 days
  (MGI Ref ID J:88807)
  • significantly activated relative to controls as measured in the anteroventricular cochlear nucleus when unilateral cochlear ablation is performed at 14 days
  (MGI Ref ID J:88807)

• decreased neuron number
  • neuronal cell loss in the anteroventricular cochlear nucleus is high relative to controls in mice operated on at 14 days
  (MGI Ref ID J:88807)
  • unilateral cochlear ablation at 21 days has little effect on neuronal cell loss in either mutant or control mice
  (MGI Ref ID J:88807)

hematopoietic system phenotype

• increased microglial cell activation
  • significantly activated relative to controls as measured in the anteroventricular cochlear nucleus when unilateral cochlear ablation is performed at 14 days
  (MGI Ref ID J:88807)
  • microglial cells seem transformed to the amoeboid activated state
  (MGI Ref ID J:88807)
  • Normal - no difference from controls if ablation performed at 21 days of age
  (MGI Ref ID J:88807)
  • no activation if cochlear ablation is performed at 5 days of age
  (MGI Ref ID J:88807)
  • level of activation is significantly higher at 4 days after operation but not at 2 or 6 days
  (MGI Ref ID J:88807)

growth/size/body region phenotype

• enlarged spleen
  (MGI Ref ID J:5579)

hematopoietic system phenotype

• increased leukocyte cell number
  (MGI Ref ID J:5579)

• small thymus
  • although smaller than normal, the thymus is histologically normal until 25 days of age
  (MGI Ref ID J:5579)
  • severe involution and necrosis is found in sick mice, with severity correlating with degree of illness
  (MGI Ref ID J:5579)

• increased IgG level
  • serum levels are elevated
  (MGI Ref ID J:5579)

• abnormal granulocyte morphology
  • differential counts of blood from 1 to 3 day old mice showed an immature granuloctye population
  (MGI Ref ID J:5579)

• abnormal thymus morphology
  (MGI Ref ID J:5579)

• enlarged spleen
  (MGI Ref ID J:5579)

• increased immunoglobulin level
  (MGI Ref ID J:5579)

• increased granulocyte number
  (MGI Ref ID J:5579)

• increased IgM level
  • serum levels are markedly elevated above normal
  (MGI Ref ID J:5579)

• increased monocyte cell number
  (MGI Ref ID J:5579)

• abnormal leukocyte cell number
  (MGI Ref ID J:5579)

• increased IgA level
  • serum levels are elevated
  (MGI Ref ID J:5579)

cellular phenotype

• abnormal cell cycle checkpoint function
  • there is a higher than normal percentage of splenocytes in S and G2/M (22% instead of 7%) and corresponding decrease in splenocytes in G0/G1 (73% instead of 89%)
  (MGI Ref ID J:66843)
  • 6 hours after 5 Gy of gamma irradiation homozygous splenocytes show abnormal cell cycle arrest, with 31% instead of the wild-type 4% in S+G2/M phases, and fewer irradiated splenocytes are found in the subG0 (hyplodiploid) state (15% instead of 45%)
  (MGI Ref ID J:66843)

• decreased apoptosis
  • B and T cells show the greatest resistance to apoptosis in the splenocyte population, but all splenic cell types including macrophages and granulocytes have greater resistance to apoptosis than wildtype cells
  (MGI Ref ID J:66843)
  • splenocytoes from homozygotes have much less disruption of mitochondrial transmembrane potential at 6 and 24 hours post-exposure to 5 Gy of gamma irradiation and do not show the normal increase in expression of Bax
  (MGI Ref ID J:66843)
  • only 21% of spleen cells are apoptotic 6 hours after exposure to 5 Gy gamma irradiation, whereas 40% of wildtype splenocytes are apoptotic after treatment.
  (MGI Ref ID J:66843)

• decreased cellular sensitivity to gamma-irradiation
  • the LD50 for homozygous spleen cells is 24.5 Gy gamma radiation versus 6.5 Gy for wildtype splenocytes
  (MGI Ref ID J:66843)

• abnormal cell cycle
  (MGI Ref ID J:66843)

immune system phenotype

• abnormal thymus morphology
  (MGI Ref ID J:5579)

• increased granulocyte number
  (MGI Ref ID J:5579)

• increased IgG level
  • serum levels are elevated
  (MGI Ref ID J:5579)

• abnormal Peyer's patch morphology
  • rarely any differentiation of lymphoid tissue into nodules is found
  (MGI Ref ID J:5579)
  • lymphocytes are larger and sparsely distributed
  (MGI Ref ID J:5579)

• enlarged spleen
  (MGI Ref ID J:5579)

• small thymus
  • severe involution and necrosis is found in sick mice, with severity correlating with degree of illness
  (MGI Ref ID J:5579)
  • although smaller than normal, the thymus is histologically normal until 25 days of age
  (MGI Ref ID J:5579)

• increased IgM level
  • serum levels are markedly elevated above normal
  (MGI Ref ID J:5579)

• autoimmune response
  • early onset
  (MGI Ref ID J:5579)

• increased IgA level
  • serum levels are elevated
  (MGI Ref ID J:5579)

• abnormal granulocyte morphology
  • differential counts of blood from 1 to 3 day old mice showed an immature granuloctye population
  (MGI Ref ID J:5579)

• abnormal immune system cell morphology
  • mice have a population of unusual binucleate lymphocytes
  (MGI Ref ID J:5579)

• increased leukocyte cell number
  (MGI Ref ID J:5579)

• abnormal leukocyte cell number
  (MGI Ref ID J:5579)

• increased monocyte cell number
  (MGI Ref ID J:5579)

• increased immunoglobulin level
  (MGI Ref ID J:5579)

• abnormal humoral immune response
  • mice are severely deficient in capacity to generate an immune response
  (MGI Ref ID J:5579)

integument phenotype

• skin lesions
  • rapidly progressing lesions develop on the feet by 3 weeks of age
  (MGI Ref ID J:5579)
  • as early as 2 days after birth abscesses appear on the skin, rupture and begin to heal in 24 hrs
  (MGI Ref ID J:5579)

• abnormal skin pigmentation
  • recognized at 3 to 4 days of age by patchy absence of skin pigment
  (MGI Ref ID J:5579)

• focal hair loss
  • patchy absence of hair in the coat gives mice a motheaten appearance
  (MGI Ref ID J:5579)

mortality/aging

• preweaning lethality, incomplete penetrance
  • high mortality before weaning
  (MGI Ref ID J:5579)

pigmentation phenotype

• abnormal skin pigmentation
  • recognized at 3 to 4 days of age by patchy absence of skin pigment
  (MGI Ref ID J:5579)

respiratory system phenotype

• abnormal lung morphology
  • mice develop lesions in the lung by 3 days of age
  (MGI Ref ID J:5579)

endocrine/exocrine gland phenotype

• small thymus
  • although smaller than normal, the thymus is histologically normal until 25 days of age
  (MGI Ref ID J:5579)
  • severe involution and necrosis is found in sick mice, with severity correlating with degree of illness
  (MGI Ref ID J:5579)

• abnormal thymus morphology
  (MGI Ref ID J:5579)