Mouse Genome Informatics
hm1
    Il4tm1Cgn/Il4tm1Cgn
B6.129P2-Il4tm1Cgn/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• survival time of cardiac allografts (BALB/c origin) is similar to wild-type mice, unlike in Ifng or Il10 null mice (J:44346)
• dendritic function is normal (J:160119)

integument
• despite normal dendritic function, mice whose backs are shaved and painted with Alexa 647-labeled ovalbumin accumulate fewer Alexa647+CD11c+ cells in draining lymph nodes compared with similarly treated wild-type mice indicating increased barrier function


Mouse Genome Informatics
hm2
    Il4tm1Cgn/Il4tm1Cgn
B6.Cg-Il4tm1Cgn
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• homozygotes display impaired pulmonary granuloma formation in response to schistosome egg immunization
• eosinophil infiltration is impaired in response to schistosome egg immunization
• IgG1 response to immunization with the protein antigen OVA is severely impaired

hematopoietic system
• homozygotes display impaired pulmonary granuloma formation in response to schistosome egg immunization
• eosinophil infiltration is impaired in response to schistosome egg immunization


Mouse Genome Informatics
hm3
    Il4tm1Cgn/Il4tm1Cgn
either: NOD.129-Il4tm1Cgn or (involves: 129 * NOD)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• at 12 weeks, insulitis incidence is similar in homozygous mutants and heterozygous controls on the NOD background (N4)

immune system
• at 12 weeks, insulitis incidence is similar in homozygous mutants and heterozygous controls on the NOD background (N4)
• there is no difference in timing or penetrance of diabetes in IL4-deficient NOD mice (N8) compared to heterozygous or wild-type NOD mice

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:85924


Mouse Genome Informatics
hm4
    Il4tm1Cgn/Il4tm1Cgn
involves: 129P2/OlaHsd * A/WySn * C57BL/10SnSg * Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• abnormal IgG responses to HgCL2 exposure
• however, mercury induced increases in autoantibodies are similar to controls

immune system
• following exposure to HgCl2 for 4 weeks, relative to similarly treated wild-type and heterozygous mice
• following exposure to HgCl2 for 4 weeks, relative to similarly treated wild-type and heterozygous mice

hematopoietic system
• following exposure to HgCl2 for 4 weeks, relative to similarly treated wild-type and heterozygous mice
• following exposure to HgCl2 for 4 weeks, relative to similarly treated wild-type and heterozygous mice


Mouse Genome Informatics
hm5
    Il4tm1Cgn/Il4tm1Cgn
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• there were no dectectable levels of IgE in 5 of 6 mice compared to controls, which all had dectectable levels
• after infection with a nematode, 6-week old animals have almost undetectable IgE levels compared to controls which show about 50-fold increase in levels after infection
• homozygotes have about 1/6 the level of IgG1 of wild-type at 6 weeks
• in response to immunization with chicken globulin, antibodies produced by mutants are ~40-50% IgG1, while wild-type mice produce >95% IgG1-specific antibodies
• conA stimulated spleen cells from homozygotes secrete ~800-fold less Il4 than control cells
• upon infection with Schistosoma mansoni eggs, primary granuloma formation and volume is equivalent to wild-type
• volumes of secondary granulomas after second exposure with parasite eggs are reduced by ~50% compared to wild-type

hematopoietic system
• there were no dectectable levels of IgE in 5 of 6 mice compared to controls, which all had dectectable levels
• after infection with a nematode, 6-week old animals have almost undetectable IgE levels compared to controls which show about 50-fold increase in levels after infection
• homozygotes have about 1/6 the level of IgG1 of wild-type at 6 weeks
• in response to immunization with chicken globulin, antibodies produced by mutants are ~40-50% IgG1, while wild-type mice produce >95% IgG1-specific antibodies


Mouse Genome Informatics
hm6
    Il4tm1Cgn/Il4tm1Cgn
involves: 129P2/OlaHsd * C57BL/6J * MRL/Mp
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• at 3 months of age relative to wild-type controls
• at 3 and 7-8 months of age relative to wild-type controls

hematopoietic system
• at 3 months of age relative to wild-type controls
• at 3 and 7-8 months of age relative to wild-type controls


Mouse Genome Informatics
hm7
    Il4tm1Cgn/Il4tm1Cgn
involves: 129P2/OlaHsd * NOD
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• CD4+ T cells from deficient animals show a reduction in circulating IgG1 in the absence of deliberate immunization
• CD4+ T cells from deficient animals show a strongly reduced ability to produce Il5 after anti-TCR stimulation compared to wild-type cells

hematopoietic system
• CD4+ T cells from deficient animals show a reduction in circulating IgG1 in the absence of deliberate immunization


Mouse Genome Informatics
hm8
    Il4tm1Cgn/Il4tm1Cgn
MRL.129P2-Il4tm1Cgn
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• dacryoadenitis, characterized by multiple foci of mononuclear inflammatory cells
• predominant cell type in infiltrate at various ages is CD4+ T cells (66%); CD8+ T cells make up 12% of infiltrate
• B cells are more abundant in infiltrates (30%) than in MRL.Cg- Il4tm1Cgn Faslpr mice

vision/eye
• dacryoadenitis, characterized by multiple foci of mononuclear inflammatory cells
• predominant cell type in infiltrate at various ages is CD4+ T cells (66%); CD8+ T cells make up 12% of infiltrate
• B cells are more abundant in infiltrates (30%) than in MRL.Cg- Il4tm1Cgn Faslpr mice

endocrine/exocrine glands
• dacryoadenitis, characterized by multiple foci of mononuclear inflammatory cells
• predominant cell type in infiltrate at various ages is CD4+ T cells (66%); CD8+ T cells make up 12% of infiltrate
• B cells are more abundant in infiltrates (30%) than in MRL.Cg- Il4tm1Cgn Faslpr mice


Mouse Genome Informatics
hm9
    Il4tm1Cgn/Il4tm1Cgn
NOD.129P2-Il4tm1Cgn
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• mice are diabetic if 2 consecutive measures of blood glucose are >240 mg/dl
• amylase activity increases slightly between 4 and 20 weeks of age (234 to 291 U/L) compared to activity in wild-type which declines
• parotid secretory protein protease activity is retained in mutants while non-diseased BALB/c animals do not show activity

endocrine/exocrine glands
• mice do not exhibit a decrease in salivary flow rates compared to NOD.B10-H2b mice at 4 weeks of age
• saliva maintains normal protein concentrations compared to NOD and NOD.B10-H2b controls

immune system
• in null females challenged with coxsackievirus B4 at 8 weeks of age, diabetes onset is not accelerated as it is in wild-type NOD females; over the 25-week follow up period, only 23% of CVB4 exposed nulls develop diabetes compared to 63% of saline-treated controls
• at 12 weeks of age, null females challenged with CVB4 develop diabetes at an accelerated rate compared with saline-treated controls (80% at 10 days after infection versus 30% of controls)

digestive/alimentary system
• mice do not exhibit a decrease in salivary flow rates compared to NOD.B10-H2b mice at 4 weeks of age
• saliva maintains normal protein concentrations compared to NOD and NOD.B10-H2b controls

Mouse Models of Human Disease
OMIM IDRef(s)
Sjogren Syndrome 270150 J:105803


Mouse Genome Informatics
hm10
    Il4tm1Cgn/Il4tm1Cgn
NOD.Cg-H2b Il4tm1Cgn
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• amylase activity increases slightly between 4 and 20 weeks of age(181 to 250 U/L) compared to activity in wild-type which decreases (386 to 288 U/L)
• parotid secretory protein protease activity is retained in mutants while non-diseased animals do not show activity

endocrine/exocrine glands
• mice do not exhibit a decrease in salivary flow rates compared to NOD.B10-H2b mice at 4 weeks of age; normal salivary flow is retained to 36 weeks of age compared to controls
• saliva maintains normal protein concentrations compared to NOD and NOD.B10-H2b controls
• foci of leukocytic infiltration contain more T cells than NOD.B10-H2b controls
• foci of leukocytic infiltration contain more T cells than NOD.B10-H2b controls

immune system
• foci of leukocytic infiltration contain more T cells than NOD.B10-H2b controls
• foci of leukocytic infiltration contain more T cells than NOD.B10-H2b controls

vision/eye
• foci of leukocytic infiltration contain more T cells than NOD.B10-H2b controls

digestive/alimentary system
• mice do not exhibit a decrease in salivary flow rates compared to NOD.B10-H2b mice at 4 weeks of age; normal salivary flow is retained to 36 weeks of age compared to controls
• saliva maintains normal protein concentrations compared to NOD and NOD.B10-H2b controls
• foci of leukocytic infiltration contain more T cells than NOD.B10-H2b controls

Mouse Models of Human Disease
OMIM IDRef(s)
Sjogren Syndrome 270150 J:105803


Mouse Genome Informatics
cx11
    Il21rtm1Wjl/Il21rtm1Wjl
Il4tm1Cgn/Il4tm1Cgn

involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• serum levels of IgGA in na´ve mice are lower than in controls
• similar defects are noted upon immunization with keyhole limpet hemocyanin (KLH)
• serum levels of IgG1 in na´ve mice are several log units lower than in controls
• these mice have severely impaired production of antigen-specific IgG1 after immunization with trinitrophenyl-conjugated chicken gamma-globulin (TNP-CGG)
• similar defects are noted upon immunization with KLH
• serum levels of IgG2a in na´ve mice are lower than in controls
• these mice have severely impaired production of antigen-specific IgG2a after immunization with TNP-CGG
• similar defects are noted upon immunization with KLH
• serum levels of IgG2b in na´ve mice are lower than in controls
• these mice have severely impaired production of antigen-specific IgG2b after immunization with TNP-CGG
• similar defects are noted upon immunization with KLH
• serum levels of IgG3 in na´ve mice are lower than in controls
• these mice have severely impaired production of antigen-specific IgG3 after immunization with TNP-CGG
• similar defects are noted upon immunization with KLH
• these mice have 10 to 20% of normal production levels of antigen-specific IgG2b after immunization with TNP-CGG
• similar defects are noted upon immunization with KLH
• lymph nodes after immunization have barely recognizable, poorly organized germinal center-like areas with scattered apoptotic cells

hematopoietic system
• serum levels of IgGA in na´ve mice are lower than in controls
• similar defects are noted upon immunization with keyhole limpet hemocyanin (KLH)
• serum levels of IgG1 in na´ve mice are several log units lower than in controls
• these mice have severely impaired production of antigen-specific IgG1 after immunization with trinitrophenyl-conjugated chicken gamma-globulin (TNP-CGG)
• similar defects are noted upon immunization with KLH
• serum levels of IgG2a in na´ve mice are lower than in controls
• these mice have severely impaired production of antigen-specific IgG2a after immunization with TNP-CGG
• similar defects are noted upon immunization with KLH
• serum levels of IgG2b in na´ve mice are lower than in controls
• these mice have severely impaired production of antigen-specific IgG2b after immunization with TNP-CGG
• similar defects are noted upon immunization with KLH
• serum levels of IgG3 in na´ve mice are lower than in controls
• these mice have severely impaired production of antigen-specific IgG3 after immunization with TNP-CGG
• similar defects are noted upon immunization with KLH
• these mice have 10 to 20% of normal production levels of antigen-specific IgG2b after immunization with TNP-CGG
• similar defects are noted upon immunization with KLH


Mouse Genome Informatics
cx12
    Il4tm1Cgn/Il4tm1Cgn
Ndfip1Gt(RRD002)Byg/Ndfip1Gt(RRD002)Byg

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• due to inflammatory disease

immune system
• increased percent in esophagus and lung mucosal tissues
• increased percent in esophagus and lung mucosal tissues
• increased percent in esophagus and lung mucosal tissues
• increased percent in esophagus and lung mucosal tissues
• compared with Il4tm1Cgn homozygotes
• at 12, but not 6, weeks

digestive/alimentary system

respiratory system

hematopoietic system
• increased percent in esophagus and lung mucosal tissues
• increased percent in esophagus and lung mucosal tissues
• increased percent in esophagus and lung mucosal tissues
• increased percent in esophagus and lung mucosal tissues


Mouse Genome Informatics
cx13
    Il4tm1Cgn/Il4tm1Cgn
Tg(CD2-Stat6*V625A*T626A)78Mhk/0

involves: 129P2/OlaHsd * C3H * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
N
• mice do not exhibit skin inflammation unlike Tg(CD2-Stat6*V625A*T626A)78Mhk mice (J:160119)
• mice exhibit normal recovery from retinoic acid treatment (J:160119)


Mouse Genome Informatics
cx14
    Il2tm1Hor/Il2tm1Hor
Il4tm1Cgn/Il4tm1Cgn

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• found in bone marrow
• B cells from lymph nodes have a larger size, and incorporate more BrdU indicating a faster proliferation rate
• found in bone marrow
• 2-10 fold higher using in vivo incorporation of BrdU, which indicates a faster proliferation rate
• there are decreased levels of viral specific antibodies 9 days after infection with lymphocytic choriomeningitis virus (J:16662)
• serum levels of IgG and IgE are close to normal in uninfected mice, compared to the high levels of these immunoglobulins found in mice with just the mutant Il2 locus (J:16662)
• there is a nine fold reduction of target cell killing by primary T cells in a chromium release assay
• there is no target cell killing by previously stimulated T cells in a chromium release assay
• footpad swelling is strongly reduced 6-10 days after infection with lymphocytic choriomeningitis virus
• despite reduced cytotoxic T cell activity, mice still eliminate lymphocytic choriomeningitis virus within nine days of infection

hematopoietic system
• found in bone marrow
• B cells from lymph nodes have a larger size, and incorporate more BrdU indicating a faster proliferation rate
• found in bone marrow
• 2-10 fold higher using in vivo incorporation of BrdU, which indicates a faster proliferation rate
• there are decreased levels of viral specific antibodies 9 days after infection with lymphocytic choriomeningitis virus (J:16662)
• serum levels of IgG and IgE are close to normal in uninfected mice, compared to the high levels of these immunoglobulins found in mice with just the mutant Il2 locus (J:16662)
• there is a nine fold reduction of target cell killing by primary T cells in a chromium release assay
• there is no target cell killing by previously stimulated T cells in a chromium release assay
• footpad swelling is strongly reduced 6-10 days after infection with lymphocytic choriomeningitis virus


Mouse Genome Informatics
cx15
    Il10tm1Cgn/Il10tm1Cgn
Il4tm1Cgn/Il4tm1Cgn

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• mice exhibit enhanced Th1 responses after infection with S. mansoni eggs compared to controls
• there is a 75-fold increase in IFN-gamma mRNA in the lungs after infection with S. mansoni eggs

hematopoietic system
• mice exhibit enhanced Th1 responses after infection with S. mansoni eggs compared to controls


Mouse Genome Informatics
cx16
    Faslpr/Faslpr
Il4tm1Cgn/Il4tm1Cgn

involves: 129P2/OlaHsd * C57BL/6J * MRL/Mp
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• lympadenopathy (based on spleen weight and cellularity) is reduced compared to mice homozygous for Faslpr and wild-type for Il4
• relative to wild-type controls but decreased relative to mice homozygous for Faslpr and wild-type for Il4
• relative to wild-type controls but decreased relative to mice homozygous for Faslpr and wild-type for Il4
• at 7-8 months of age relative to mice homozygous for Faslpr and wild-type for Il4
• at 3 and 7-8 months of age relative to mice homozygous for Faslpr and wild-type for Il4
• at 3 and 7-8 months of age relative to mice homozygous for Faslpr and wild-type for Il4
• at 7-8 months of age relative to mice homozygous for Faslpr and wild-type for Il4
• lympadenopathy (based on lymph node weight and cellularity) is reduced compared to mice homozygous for Faslpr and wild-type for Il4
• while mice develop the typical autoimmune lesions end organ disease is decreased compared to mice homozygous for Faslpr and wild-type for Ifng
• incidence of end organ disease is increased compared to wild-type controls
• decrease in the percentage of FANA positive sera compared to controls at 3 months of age
• however, no significant differences in anti-dsDNA or anti-snRNP autoantibody levels are detected

homeostasis/metabolism
• levels are lower compared to mice homozygous for Faslpr and wild-type for Il4

hematopoietic system
• lympadenopathy (based on spleen weight and cellularity) is reduced compared to mice homozygous for Faslpr and wild-type for Il4
• relative to wild-type controls but decreased relative to mice homozygous for Faslpr and wild-type for Il4
• relative to wild-type controls but decreased relative to mice homozygous for Faslpr and wild-type for Il4
• at 7-8 months of age relative to mice homozygous for Faslpr and wild-type for Il4
• at 3 and 7-8 months of age relative to mice homozygous for Faslpr and wild-type for Il4
• at 3 and 7-8 months of age relative to mice homozygous for Faslpr and wild-type for Il4
• at 7-8 months of age relative to mice homozygous for Faslpr and wild-type for Il4


Mouse Genome Informatics
cx17
    Faslpr/Faslpr
Il4tm1Cgn/Il4tm1Cgn

MRL.Cg-Il4tm1Cgn Faslpr
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• dacryoadenitis, characterized by multiple foci of mononuclear inflammatory cells
• predominant cell type in infiltrate at various ages is CD4+ T cells (66%); CD8+ T cells make up 16% of infiltrate
• B cells are somewhat less abundant in infiltrates (18%) than in double mutants
• less severe than MRL/MpJ-Faslpr mice at 3 and 5 months

renal/urinary system
• less severe than MRL/MpJ-Faslpr mice at 3 and 5 months

vision/eye
• dacryoadenitis, characterized by multiple foci of mononuclear inflammatory cells
• predominant cell type in infiltrate at various ages is CD4+ T cells (66%); CD8+ T cells make up 16% of infiltrate
• B cells are somewhat less abundant in infiltrates (18%) than in double mutants

endocrine/exocrine glands
• dacryoadenitis, characterized by multiple foci of mononuclear inflammatory cells
• predominant cell type in infiltrate at various ages is CD4+ T cells (66%); CD8+ T cells make up 16% of infiltrate
• B cells are somewhat less abundant in infiltrates (18%) than in double mutants


Mouse Genome Informatics
cx18
    Il4tm1Cgn/Il4tm1Cgn
Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0

NOD.Cg-Il4tm1Cgn Tg(TcraBDC2.5,TcrbBDC2.5)1Doi
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• equal degrees of insulitis are detected at 5 weeks in transgenic IL4-deficient NOD mice and control transgenic NOD mice

immune system
• equal degrees of insulitis are detected at 5 weeks in transgenic IL4-deficient NOD mice and control transgenic NOD mice
• Il4-deficient transgenic NOD mice do not show early or frequent diabetes compared to control transgenic NOD mice

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:85924