Mouse Genome Informatics
hm1
    Ptpn6me/Ptpn6me
C3FeLe.B6 a/a-Ptpn6me/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• significantly activated relative to controls as measured in the anteroventricular cochlear nucleus when unilateral cochlear ablation is performed at 14 days
• microglial cells seem transformed to the amoeboid activated state
• level of activation is significantly higher at 4 days after operation but not at 2 or 6 days
• no activation if cochlear ablation is performed at 5 days of age
• no difference from controls if ablation performed at 21 days of age
• neuronal cell loss in the anteroventricular cochlear nucleus is high relative to controls in mice operated on at 14 days
• unilateral cochlear ablation at 21 days has little effect on neuronal cell loss in either mutant or control mice

immune system
• significantly activated relative to controls as measured in the anteroventricular cochlear nucleus when unilateral cochlear ablation is performed at 14 days
• microglial cells seem transformed to the amoeboid activated state
• level of activation is significantly higher at 4 days after operation but not at 2 or 6 days
• no activation if cochlear ablation is performed at 5 days of age
• no difference from controls if ablation performed at 21 days of age

hematopoietic system
• significantly activated relative to controls as measured in the anteroventricular cochlear nucleus when unilateral cochlear ablation is performed at 14 days
• microglial cells seem transformed to the amoeboid activated state
• level of activation is significantly higher at 4 days after operation but not at 2 or 6 days
• no activation if cochlear ablation is performed at 5 days of age
• no difference from controls if ablation performed at 21 days of age


Mouse Genome Informatics
hm2
    Ptpn6me/Ptpn6me
C57BL/6J-Ptpn6me/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• high mortality before weaning

pigmentation
• recognized at 3 to 4 days of age by patchy absence of skin pigment

immune system
• although smaller than normal, the thymus is histologically normal until 25 days of age
• severe involution and necrosis is found in sick mice, with severity correlating with degree of illness
• mice have a population of unusual binucleate lymphocytes
• differential counts of blood from 1 to 3 day old mice showed an immature granuloctye population
• rarely any differentiation of lymphoid tissue into nodules is found
• lymphocytes are larger and sparsely distributed
• mice are deficient in capacity for immune response
• serum levels are elevated
• serum levels are elevated
• serum levels are markedly elevated above normal

hematopoietic system
• although smaller than normal, the thymus is histologically normal until 25 days of age
• severe involution and necrosis is found in sick mice, with severity correlating with degree of illness
• differential counts of blood from 1 to 3 day old mice showed an immature granuloctye population
• serum levels are elevated
• serum levels are elevated
• serum levels are markedly elevated above normal

respiratory system
• mice develop lesions in the lung by 3 days of age

cellular
• 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%)
• 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%)
• 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.
• 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
• 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
• the LD50 for homozygous spleen cells is 24.5 Gy gamma radiation versus 6.5 Gy for wildtype splenocytes

integument
• patchy absence of hair in the coat gives mice a motheaten appearance
• rapidly progressing lesions develop on the feet by 3 weeks of age
• as early as 2 days after birth abscesses appear on the skin, rupture and begin to heal in 24 hrs
• recognized at 3 to 4 days of age by patchy absence of skin pigment

endocrine/exocrine glands
• although smaller than normal, the thymus is histologically normal until 25 days of age
• severe involution and necrosis is found in sick mice, with severity correlating with degree of illness


Mouse Genome Informatics
hm3
    Ptpn6me/Ptpn6me
involves: C3H/HeN * C57BL/6J * NFS
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: life span about 8 weeks whereas on a C57BL/6 background survival is about 3 weeks
• Background Sensitivity: occasional survival to 16 weeks on an NFS or C3H background for larger individuals

growth/size
• weigh about 66% of control weight

limbs/digits/tail
• autoamputation of 2-3 extremities by 8 weeks of age

integument
• cutaneous granulomatous lesions at 8 weeks

cellular
• lack of stimulatory effect of ConA

hematopoietic system
• lack of stimulatory effect of ConA
• increased secretion by splenocytes in culture
• serum levels elevated relative to controls

immune system
• lack of stimulatory effect of ConA
• increased secretion by splenocytes in culture
• serum levels elevated relative to controls


Mouse Genome Informatics
hm4
    Ptpn6me/Ptpn6me
involves: C3HeB/FeJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• death at around 3 weeks of age involving intra alveolar hemorrhage

growth/size
• about half of controls

nervous system
• length and width decreased
• weight normal
• scattered areas of focal necrosis
• scattered areas of focal necrosis in the cortex
• about 20% more neurons present
• F4/80+ microglial cells are reduced in number
• GFAP+ astrocytes decreased about 50% on both the hippocampus and the forebrain fiber tracts
• decreased

respiratory system
• intra alveolar hemorrhage around 3 weeks of age leading to death

hematopoietic system
• F4/80+ microglial cells are reduced in number

immune system
• F4/80+ microglial cells are reduced in number


Mouse Genome Informatics
cx5
    Btkxid/?
Ptpn6me/Ptpn6me

involves: C57BL/6J * CBA/N * NFS
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: life span about 8 weeks whereas on a C57BL/6 background survival is about 3 weeks

growth/size
• weigh about 66% of control weight

limbs/digits/tail
• autoamputation of 2-3 extremities by 8 weeks of age

integument
• cutaneous granulomatous lesions at 8 weeks

immune system
• lack of stimulatory effect of ConA
• increased secretion by splenocytes in culture
• serum levels considerably lower than Ptpn6me/me controls
• very slightly elevated relative to controls

cellular
• lack of stimulatory effect of ConA

hematopoietic system
• lack of stimulatory effect of ConA
• increased secretion by splenocytes in culture
• serum levels considerably lower than Ptpn6me/me controls