Phenotypes associated with this allele

• Allele Symbol: Il21r^tm1Wjl
• Allele Name: targeted mutation 1, Warren J Leonard
• Allele ID: MGI:2446509
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Il21r^tm1Wjl/Il21r^tm1Wjl	involves: 129 * C57BL/6	MGI:3813931
hm2	Il21r^tm1Wjl/Il21r^tm1Wjl	NOD.Cg-Il21r^tm1Wjl	MGI:3814064
cx3	Il21r^tm1Wjl/Il21r^tm1Wjl X/Yaa	BXSB.129(Cg)-Il21r^tm1Wjl/Dcr	MGI:3835838
cx4	Il21r^tm1Wjl/Il21r^tm1Wjl Il4^tm1Cgn/Il4^tm1Cgn	involves: 129 * C57BL/6	MGI:3813932

Genotype
MGI:3813931

hm1

• Allelic Composition: Il21r^tm1Wjl/Il21r^tm1Wjl
• Genetic Background: involves: 129 * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

immune system

abnormal immunoglobulin level ( J:80474 )

increased IgE level ( J:80474 )

• serum levels of IgE in nave mice are higher than in controls

• ovalbumin immunized mice have variable total IgE levels with some mice having levels similar to wild-type and some mice having 3- to 6- fold higher amounts

• total IgE production is increased about 50-fold after KLH immunization with similar increases with antigen specific antibody

• IgE levels are 20- to 25- fold greater than controls 100 days after infection with toxoplasma gondii

decreased IgG1 level ( J:80474 )

• serum levels of IgG1 in nave mice are lower than in controls

• after immunization with ovalbumin, the normal increase in IgG1 seen in wild-type mice is markedly impaired in these mice

• in immunized mice, total serum IgG1 is 4 to 5% of wild-type and levels of antigen-specific antibody is 0.1% of that in wild-type

• an impaired IgG1 response is also observed after keyhole limpet hemocyanin (KLH) immunization, with antigen specific antibodies being 1/10 of that found in wild-type

• IgG1 levels are third of controls 100 days after infection with toxoplasma gondii

decreased IgG2a level ( J:80474 )

• IgG2a levels are lower than controls 100 days after infection with toxoplasma gondii

decreased IgG2b level ( J:80474 )

• serum levels of IgG2b in nave mice are lower than in controls

• after ovalbumin immunization, levels of antigen specific IgGb2 antibody are significantly lower

• an impaired IgG2b response is also observed after KLH immunization, with antigen specific antibodies being 1/10 of that found in wild-type

• IgG2b levels are lower than controls 100 days after infection with toxoplasma gondii

decreased IgG3 level ( J:80474 )

• after ovalbumin immunization, levels of antigen specific IgG3 antibody are significantly lower

• an impaired IgG3 response is also observed after KLH immunization, with antigen specific antibodies being 1/10 of that found in wild-type

• IgG3 levels are lower than controls 100 days after infection with toxoplasma gondii

abnormal CD8-positive, alpha-beta T cell physiology ( J:95221 )

• CD8⁺ T cell proliferation in vitro is not enhanced in the presence of IL-15 in the same manner as wild-type CD8⁺ T cells

• the percentage of antigen-specific CD8⁺ T cells found in the spleen is a third lower than controls after vaccination

• the percentage of CD8⁺ T cells making IFN-gamma one week after vaccination is about half that of wild-type controls

decreased cytotoxic T cell cytolysis ( J:95221 )

• the cytotoxic activity of CD8⁺ T cells is significantly lower than wild-type cells

decreased interleukin-17 secretion ( J:124293 )

• IL-17 production by CD4 T cells is much lower than controls when activated with IL-6 and TGF-beta in vitro

• there is no IL-17 production from T cells when activated in vitro with IL-21 and TGF-beta compared to the robust production of controls

hematopoietic system

abnormal immunoglobulin level ( J:80474 )

increased IgE level ( J:80474 )

• serum levels of IgE in nave mice are higher than in controls

• ovalbumin immunized mice have variable total IgE levels with some mice having levels similar to wild-type and some mice having 3- to 6- fold higher amounts

• total IgE production is increased about 50-fold after KLH immunization with similar increases with antigen specific antibody

• IgE levels are 20- to 25- fold greater than controls 100 days after infection with toxoplasma gondii

decreased IgG1 level ( J:80474 )

• serum levels of IgG1 in nave mice are lower than in controls

• after immunization with ovalbumin, the normal increase in IgG1 seen in wild-type mice is markedly impaired in these mice

• in immunized mice, total serum IgG1 is 4 to 5% of wild-type and levels of antigen-specific antibody is 0.1% of that in wild-type

• an impaired IgG1 response is also observed after keyhole limpet hemocyanin (KLH) immunization, with antigen specific antibodies being 1/10 of that found in wild-type

• IgG1 levels are third of controls 100 days after infection with toxoplasma gondii

decreased IgG2a level ( J:80474 )

• IgG2a levels are lower than controls 100 days after infection with toxoplasma gondii

decreased IgG2b level ( J:80474 )

• serum levels of IgG2b in nave mice are lower than in controls

• after ovalbumin immunization, levels of antigen specific IgGb2 antibody are significantly lower

• an impaired IgG2b response is also observed after KLH immunization, with antigen specific antibodies being 1/10 of that found in wild-type

• IgG2b levels are lower than controls 100 days after infection with toxoplasma gondii

decreased IgG3 level ( J:80474 )

• after ovalbumin immunization, levels of antigen specific IgG3 antibody are significantly lower

• an impaired IgG3 response is also observed after KLH immunization, with antigen specific antibodies being 1/10 of that found in wild-type

• IgG3 levels are lower than controls 100 days after infection with toxoplasma gondii

abnormal CD8-positive, alpha-beta T cell physiology ( J:95221 )

• CD8⁺ T cell proliferation in vitro is not enhanced in the presence of IL-15 in the same manner as wild-type CD8⁺ T cells

• the percentage of antigen-specific CD8⁺ T cells found in the spleen is a third lower than controls after vaccination

• the percentage of CD8⁺ T cells making IFN-gamma one week after vaccination is about half that of wild-type controls

decreased cytotoxic T cell cytolysis ( J:95221 )

• the cytotoxic activity of CD8⁺ T cells is significantly lower than wild-type cells

Genotype
MGI:3814064

hm2

• Allelic Composition: Il21r^tm1Wjl/Il21r^tm1Wjl
• Genetic Background: NOD.Cg-Il21r^tm1Wjl

immune system

decreased T cell proliferation ( J:139075 )

• T cells isolated from pancreatic lymph nodes have about 25% less proliferative response when activated in vitro

abnormal CD4-positive T cell differentiation ( J:139075 )

• about a third to a half less Th17 T cells are produced when CD4⁺ T cells isolated from either spleen or pancreatic lymph nodes are cultured under Th17-polarizing conditions

decreased interleukin-17 secretion ( J:139075 )

• CD4⁺ T cells produce half to three-quarter less IL-17 than controls when stimulated in vitro

• CD4⁺ T cells cultured under Th17-polarizing conditions also produce much less IL-17 than controls

decreased susceptibility to autoimmune diabetes ( J:139075 )

• only 5% of mice develop diabetes (determined by blood glucose being greater than 250mg/dl) compared to 60% of NOD mice not carrying the mutant allele

• 12-week old mice lack inflammatory infiltration of the pancreas islet cells as is typically found in age-matched NOD controls

hematopoietic system

decreased T cell proliferation ( J:139075 )

• T cells isolated from pancreatic lymph nodes have about 25% less proliferative response when activated in vitro

abnormal CD4-positive T cell differentiation ( J:139075 )

• about a third to a half less Th17 T cells are produced when CD4⁺ T cells isolated from either spleen or pancreatic lymph nodes are cultured under Th17-polarizing conditions

cellular

decreased T cell proliferation ( J:139075 )

• T cells isolated from pancreatic lymph nodes have about 25% less proliferative response when activated in vitro

Genotype
MGI:3835838

cx3

• Allelic Composition: Il21r^tm1Wjl/Il21r^tm1Wjl; X/Yaa
• Genetic Background: BXSB.129(Cg)-Il21r^tm1Wjl/Dcr

immune system

decreased susceptibility to systemic lupus erythematosus ( J:144484 )

♂

mortality/aging

mortality/aging ( J:144484 , J:179430 )

♂N • the hypergammaglobulinemia, autoantibody production, reduced frequencies of marginal zone B cells and monocytosis, renal disease, and premature morbidity that are found in Yaa bearing mice with at least one wildtype copy of the interleukin 21 receptor are ameliorated or prevented by the disruption of the interleukin 21 receptor (J:144484)

♂N • unlike IL21R heterozygous B2M null controls, these double homozygotes do not develop the Lupus-like autoimmune syndrome caused by Yaa and generally survive beyond 40 weeks of age (J:179430)

Genotype
MGI:3813932

cx4

• Allelic Composition: Il21r^tm1Wjl/Il21r^tm1Wjl; Il4^tm1Cgn/Il4^tm1Cgn
• Genetic Background: involves: 129 * C57BL/6

immune system

abnormal immunoglobulin level ( J:80474 )

decreased IgA level ( J:80474 )

• serum levels of IgGA in nave mice are lower than in controls

• similar defects are noted upon immunization with keyhole limpet hemocyanin (KLH)

decreased IgG1 level ( J:80474 )

• serum levels of IgG1 in nave 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

decreased IgG2a level ( J:80474 )

• serum levels of IgG2a in nave 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

decreased IgG2b level ( J:80474 )

• serum levels of IgG2b in nave 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

decreased IgG3 level ( J:80474 )

• serum levels of IgG3 in nave 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

decreased IgM level ( J:80474 )

• 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

abnormal lymph node germinal center morphology ( J:80474 )

• lymph nodes after immunization have barely recognizable, poorly organized germinal center-like areas with scattered apoptotic cells

hematopoietic system

abnormal immunoglobulin level ( J:80474 )

decreased IgA level ( J:80474 )

• serum levels of IgGA in nave mice are lower than in controls

• similar defects are noted upon immunization with keyhole limpet hemocyanin (KLH)

decreased IgG1 level ( J:80474 )

• serum levels of IgG1 in nave 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

decreased IgG2a level ( J:80474 )

• serum levels of IgG2a in nave 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

decreased IgG2b level ( J:80474 )

• serum levels of IgG2b in nave 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

decreased IgG3 level ( J:80474 )

• serum levels of IgG3 in nave 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

decreased IgM level ( J:80474 )

• 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