Phenotypes associated with this allele

• Allele Symbol: Il2rg^tm1Cgn
• Allele Name: targeted mutation 1, University of Cologne
• Allele ID: MGI:1861947
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Il2rg^tm1Cgn/Il2rg^tm1Cgn	involves: 129 * CB20	MGI:2179821
cx2	Il2rg^tm1Cgn/Y Rag2^tm1Fwa/Rag2^tm1Fwa	B6.129-Rag2^tm1Fwa Il2rg^tm1Cgn	MGI:3776480
cx3	Il2rg^tm1Cgn/Il2rg^tm1Cgn Kit^tm1.1Bsm/Kit^tm1.1Bsm	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6	MGI:4358484
cx4	Il2rg^tm1Cgn/Il2rg^tm1Cgn Rag2^tm1Fwa/Rag2^tm1Fwa	involves: 129P2/OlaHsd * 129S/SvEv	MGI:3829712
cx5	Rag2^tm1Fwa/Rag2^tm1Fwa Cd47^tm1Fpl/Cd47^tm1Fpl Il2rg^tm1Cgn/Y	involves: 129P2/OlaHsd * 129S/SvEv * 129S7/SvEvBrd * C57BL/6	MGI:5538575
ot6	Il2rg^tm1Cgn/Y	involves: 129 * CB20	MGI:2179823

Genotype
MGI:2179821

hm1

• Allelic Composition: Il2rg^tm1Cgn/Il2rg^tm1Cgn
• Genetic Background: involves: 129 * CB20

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

immune system

decreased T cell proliferation ( J:22521 )

♀ • splenic T cells do not proliferate in response to Con A

thymus hypoplasia ( J:22521 )

♀ • 22-fold reduction in cellularity

abnormal thymocyte activation ( J:22521 )

♀ • thymocytes do not activate in response to Con A

abnormal leukocyte morphology ( J:22521 )

♀

abnormal class switch recombination ( J:22521 )

♀ • in vitro class switch using LPS and IL-4 fail to generate more IgG1-positive cells

decreased mature B cell number ( J:22521 )

♀ • 12-fold reduction in the spleen in 3-4 week old mice

♀ • further loss occurs with age

decreased plasma cell number ( J:22521 )

♀ • plasma cells in the gut are exceptionally rare

decreased pre-B cell number ( J:22521 )

♀ • 20-fold decrease in bone marrow though some cells are still present

absent NK cells ( J:22521 )

♀ • NK cells are not detected in the spleen

decreased T cell number ( J:22521 )

♀ • 3 fold reduction of mature alphabeta T cells in the spleen

♀ • reduction of T cells in lamina propia of gut is observed

abnormal alpha-beta intraepithelial T cell morphology ( J:22521 )

♀ • 12-fold reduction in number of T cells found in gut epithelium

spleen hypoplasia ( J:22521 )

♀ • 8-fold reduction in cellularity

absent spleen germinal center ( J:22521 )

♀ • no germinal centers are observed

decreased spleen white pulp amount ( J:22521 )

♀ • clusters of white pulp are diminished in number and size

decreased IgE level ( J:22521 )

♀ • no IgE detected in the sera

decreased IgM level ( J:22521 )

♀ • 3-fold reduction in sera levels

impaired natural killer cell mediated cytotoxicity ( J:22521 )

♀ • no splenic NK killing activity is observed against a NK-sensitive target cell line

absent Peyer's patches ( J:22521 )

♀ • Peyer's patchers are not observed

hematopoietic system

decreased T cell proliferation ( J:22521 )

♀ • splenic T cells do not proliferate in response to Con A

abnormal thymocyte activation ( J:22521 )

♀ • thymocytes do not activate in response to Con A

abnormal hematopoietic system morphology/development ( J:22521 )

♀

thymus hypoplasia ( J:22521 )

♀ • 22-fold reduction in cellularity

abnormal leukocyte morphology ( J:22521 )

♀

abnormal class switch recombination ( J:22521 )

♀ • in vitro class switch using LPS and IL-4 fail to generate more IgG1-positive cells

decreased mature B cell number ( J:22521 )

♀ • 12-fold reduction in the spleen in 3-4 week old mice

♀ • further loss occurs with age

decreased plasma cell number ( J:22521 )

♀ • plasma cells in the gut are exceptionally rare

decreased pre-B cell number ( J:22521 )

♀ • 20-fold decrease in bone marrow though some cells are still present

absent NK cells ( J:22521 )

♀ • NK cells are not detected in the spleen

decreased T cell number ( J:22521 )

♀ • 3 fold reduction of mature alphabeta T cells in the spleen

♀ • reduction of T cells in lamina propia of gut is observed

abnormal alpha-beta intraepithelial T cell morphology ( J:22521 )

♀ • 12-fold reduction in number of T cells found in gut epithelium

spleen hypoplasia ( J:22521 )

♀ • 8-fold reduction in cellularity

absent spleen germinal center ( J:22521 )

♀ • no germinal centers are observed

decreased spleen white pulp amount ( J:22521 )

♀ • clusters of white pulp are diminished in number and size

decreased IgE level ( J:22521 )

♀ • no IgE detected in the sera

decreased IgM level ( J:22521 )

♀ • 3-fold reduction in sera levels

impaired natural killer cell mediated cytotoxicity ( J:22521 )

♀ • no splenic NK killing activity is observed against a NK-sensitive target cell line

endocrine/exocrine glands

thymus hypoplasia ( J:22521 )

♀ • 22-fold reduction in cellularity

abnormal thymocyte activation ( J:22521 )

♀ • thymocytes do not activate in response to Con A

cellular

decreased T cell proliferation ( J:22521 )

♀ • splenic T cells do not proliferate in response to Con A

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	combined T cell and B cell immunodeficiency	DOID:628		J:22521
NOT	X-linked severe combined immunodeficiency	DOID:0060013	OMIM:300400	J:22521

Genotype
MGI:3776480

cx2

• Allelic Composition: Il2rg^tm1Cgn/Y; Rag2^tm1Fwa/Rag2^tm1Fwa
• Genetic Background: B6.129-Rag2^tm1Fwa Il2rg^tm1Cgn

immune system

absent B cells ( J:132257 )

♂ • mice lack all B cells

absent NK cells ( J:132257 )

♂ • mice lack all NK cells

♂ • NK cells that are transferred into these mice are able to proliferate with a lifespan of about 10 days

absent T cells ( J:132257 )

♂ • mice lack all T cells

hematopoietic system

absent B cells ( J:132257 )

♂ • mice lack all B cells

absent NK cells ( J:132257 )

♂ • mice lack all NK cells

♂ • NK cells that are transferred into these mice are able to proliferate with a lifespan of about 10 days

absent T cells ( J:132257 )

♂ • mice lack all T cells

Genotype
MGI:4358484

cx3

• Allelic Composition: Il2rg^tm1Cgn/Il2rg^tm1Cgn; Kit^tm1.1Bsm/Kit^tm1.1Bsm
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6

hematopoietic system

arrested T cell differentiation ( J:90485 )

♀ • similar to in Il2rg^tm1Cgn homozygotes, T cell development is blocked at the TN3 to TN4 stage

immune system

arrested T cell differentiation ( J:90485 )

♀ • similar to in Il2rg^tm1Cgn homozygotes, T cell development is blocked at the TN3 to TN4 stage

Genotype
MGI:3829712

cx4

• Allelic Composition: Il2rg^tm1Cgn/Il2rg^tm1Cgn; Rag2^tm1Fwa/Rag2^tm1Fwa
• Genetic Background: involves: 129P2/OlaHsd * 129S/SvEv

immune system

decreased NK cell number ( J:142654 )

♀ • Ncr(NKp46)⁺ NK1.1⁺ NK cells are essentially absent

♀ • the NKp46⁺CD127⁺ NK1.1^- subset of intestinal natural killer cells is also absent

abnormal interleukin secretion ( J:142654 )

♀ • there is no interleukin 22 (IL-22) secretion by colonic lamina propia cells isolated from mice infected with C. rodentium compared to controls that secrete detectable amounts of IL-22

increased susceptibility to bacterial infection ( J:142654 )

♀ • mice are extremely susceptible to C. rodentium infection, with all mice showing dramatic weight loss and succumbing to infection by day 7

♀ • controls (Rag2 knockouts, Rag2 and Il2rg double knockouts) are not susceptible to infection

hematopoietic system

decreased NK cell number ( J:142654 )

♀ • Ncr(NKp46)⁺ NK1.1⁺ NK cells are essentially absent

♀ • the NKp46⁺CD127⁺ NK1.1^- subset of intestinal natural killer cells is also absent

Genotype
MGI:5538575

cx5

• Allelic Composition: Rag2^tm1Fwa/Rag2^tm1Fwa; Cd47^tm1Fpl/Cd47^tm1Fpl; Il2rg^tm1Cgn/Y
• Genetic Background: involves: 129P2/OlaHsd * 129S/SvEv * 129S7/SvEvBrd * C57BL/6

immune system

increased CD8-positive, alpha-beta T cell number ( J:203904 )

• HIV-infected BLT transplanted mice exhibit a loss of CD4+ T cells and an increase in CD8+ T cells

increased activated T cell number ( J:203904 )

• a high proportion of CD38+ CD8+ T cells appear activated in HIV-infected BLT transplanted mice

decreased lymphocyte cell number ( J:203904 )

• spleen and lymph nodes lack lymphocytes

decreased CD4-positive, alpha-beta T cell number ( J:203904 )

• HIV-infected BLT transplanted mice exhibit a loss of CD4+ T cells and an increase in CD8+ T cells

absent peripheral lymph nodes ( J:203904 )

• mice fail to develop peripheral lymph nodes

increased susceptibility to Retroviridae infection ( J:203904 )

• 54% of BLT transplanted mice inoculated intrarectally with HIV become infected with plasma viral titers peaking between 2 and 4 weeks

• 100% of transplanted mice inoculated intraperitoneally with HIV become infected

• HIV-infected BLT transplanted mice exhibit a loss of CD4+ T cells and an increase in CD8+ T cells

• a high proportion of CD8+ T cells appear activated in HIV-infected BLT transplanted mice

• infected mice produce HIV-specific antibodies and can mount HIV-specific T cell responses

decreased susceptibility to graft versus host disease ( J:203904 )

• mice are tolerized to xenotransplantation with human bone marrow, liver, thymus (BLT)

• mice average 1x10⁶ human leukocytes/mL blood 12 weeks after transplantation and levels remain stable or improve through 21 weeks

• >80% of leukocytes in peripheral circulation are human

• transplanted mice have higher levels of multipotent bone marrow/hematopoietic stem cells than mice heterozygous for the Cd47^tm1Fpl allele

• GVHD is not evident in mice 25 weeks post-transplantation

• human thymic organoids are highly vascularized

• large and small intestines of transplanted mice contain CD4+ and CD8+ human T cells

hematopoietic system

increased CD8-positive, alpha-beta T cell number ( J:203904 )

• HIV-infected BLT transplanted mice exhibit a loss of CD4+ T cells and an increase in CD8+ T cells

increased activated T cell number ( J:203904 )

• a high proportion of CD38+ CD8+ T cells appear activated in HIV-infected BLT transplanted mice

decreased lymphocyte cell number ( J:203904 )

• spleen and lymph nodes lack lymphocytes

decreased CD4-positive, alpha-beta T cell number ( J:203904 )

• HIV-infected BLT transplanted mice exhibit a loss of CD4+ T cells and an increase in CD8+ T cells

Genotype
MGI:2179823

ot6

• Allelic Composition: Il2rg^tm1Cgn/Y
• Genetic Background: involves: 129 * CB20

immune system

decreased T cell proliferation ( J:22521 )

♂ • splenic T cells do not proliferate in response to Con A

thymus hypoplasia ( J:22521 , J:111821 )

♂ • 22-fold reduction in cellularity (J:22521)

♂ • 10-fold less cellularity of thymus from fetal day E15.5 through birth (J:111821)

♂ • 20-fold less cellularity by six days of age (J:111821)

abnormal thymocyte activation ( J:22521 )

♂ • thymocytes do not activate in response to Con A

abnormal leukocyte morphology ( J:22521 )

♂

abnormal class switch recombination ( J:22521 )

♂ • in vitro class switch using LPS and IL-4 fail to generate more IgG1-positive cells

abnormal gamma-delta T cell differentiation ( J:111821 )

♂ • complete absence of gamma-delta T cells in adult thymus

♂ • few gamma-delta T cells found in fetal thymus

♂ • TCR-gamma rearrangements are severely reduced

decreased mature B cell number ( J:22521 )

♂ • 12-fold reduction in the spleen in 3-4 week old mice

♂ • further loss occurs with age

decreased plasma cell number ( J:22521 )

♂ • plasma cells in the gut are exceptionally rare

decreased pre-B cell number ( J:22521 )

♂ • 20-fold decrease in bone marrow though some cells are still present

absent NK cells ( J:22521 )

♂ • NK cells are not detected in the spleen

decreased T cell number ( J:22521 )

♂ • 3 fold reduction of mature alphabeta T cells in the spleen

♂ • reduction of T cells in lamina propia of gut is observed

absent gamma-delta T cells ( J:111821 )

♂ • no gamma-delta T cells are found in peripheral lymphnoid organs or skin

absent gamma-delta intraepithelial T cell ( J:111821 )

♂

abnormal alpha-beta intraepithelial T cell morphology ( J:22521 )

♂ • 12-fold reduction in number of T cells found in gut epithelium

spleen hypoplasia ( J:22521 )

♂ • 8-fold reduction in cellularity

absent spleen germinal center ( J:22521 )

♂ • no germinal centers are observed

decreased spleen white pulp amount ( J:22521 )

♂ • clusters of white pulp are diminished in number and size

decreased IgE level ( J:22521 )

♂ • no IgE detected in the sera

decreased IgM level ( J:22521 )

♂ • 3-fold reduction in sera levels

impaired natural killer cell mediated cytotoxicity ( J:22521 )

♂ • no splenic NK killing activity is observed against a NK-sensitive target cell line

absent Peyer's patches ( J:22521 )

♂ • Peyer's patchers are not observed

hematopoietic system

decreased T cell proliferation ( J:22521 )

♂ • splenic T cells do not proliferate in response to Con A

thymus hypoplasia ( J:22521 , J:111821 )

♂ • 22-fold reduction in cellularity (J:22521)

♂ • 10-fold less cellularity of thymus from fetal day E15.5 through birth (J:111821)

♂ • 20-fold less cellularity by six days of age (J:111821)

abnormal thymocyte activation ( J:22521 )

♂ • thymocytes do not activate in response to Con A

abnormal leukocyte morphology ( J:22521 )

♂

abnormal class switch recombination ( J:22521 )

♂ • in vitro class switch using LPS and IL-4 fail to generate more IgG1-positive cells

abnormal gamma-delta T cell differentiation ( J:111821 )

♂ • complete absence of gamma-delta T cells in adult thymus

♂ • few gamma-delta T cells found in fetal thymus

♂ • TCR-gamma rearrangements are severely reduced

decreased mature B cell number ( J:22521 )

♂ • 12-fold reduction in the spleen in 3-4 week old mice

♂ • further loss occurs with age

decreased plasma cell number ( J:22521 )

♂ • plasma cells in the gut are exceptionally rare

decreased pre-B cell number ( J:22521 )

♂ • 20-fold decrease in bone marrow though some cells are still present

absent NK cells ( J:22521 )

♂ • NK cells are not detected in the spleen

decreased T cell number ( J:22521 )

♂ • 3 fold reduction of mature alphabeta T cells in the spleen

♂ • reduction of T cells in lamina propia of gut is observed

absent gamma-delta T cells ( J:111821 )

♂ • no gamma-delta T cells are found in peripheral lymphnoid organs or skin

absent gamma-delta intraepithelial T cell ( J:111821 )

♂

abnormal alpha-beta intraepithelial T cell morphology ( J:22521 )

♂ • 12-fold reduction in number of T cells found in gut epithelium

spleen hypoplasia ( J:22521 )

♂ • 8-fold reduction in cellularity

absent spleen germinal center ( J:22521 )

♂ • no germinal centers are observed

decreased spleen white pulp amount ( J:22521 )

♂ • clusters of white pulp are diminished in number and size

decreased IgE level ( J:22521 )

♂ • no IgE detected in the sera

decreased IgM level ( J:22521 )

♂ • 3-fold reduction in sera levels

impaired natural killer cell mediated cytotoxicity ( J:22521 )

♂ • no splenic NK killing activity is observed against a NK-sensitive target cell line

endocrine/exocrine glands

thymus hypoplasia ( J:22521 , J:111821 )

♂ • 22-fold reduction in cellularity (J:22521)

♂ • 10-fold less cellularity of thymus from fetal day E15.5 through birth (J:111821)

♂ • 20-fold less cellularity by six days of age (J:111821)

abnormal thymocyte activation ( J:22521 )

♂ • thymocytes do not activate in response to Con A

cellular

decreased T cell proliferation ( J:22521 )

♂ • splenic T cells do not proliferate in response to Con A

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	combined T cell and B cell immunodeficiency	DOID:628		J:22521
NOT	X-linked severe combined immunodeficiency	DOID:0060013	OMIM:300400	J:22521