Phenotypes associated with this allele

• Allele Symbol: Nfkb2^tm2Brv
• Allele Name: targeted mutation 2, Rodrigo Bravo
• Allele ID: MGI:2180306
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nfkb2^tm2Brv/Nfkb2^tm2Brv	involves: 129S1/Sv	MGI:5441220
hm2	Nfkb2^tm2Brv/Nfkb2^tm2Brv	involves: 129S1/Sv * C57BL/6	MGI:4352675
cx3	Nfkb2^tm2Brv/Nfkb2^tm2Brv Tg(Tnfsf13b)1Fma/?	B6.Cg-Nfkb2^tm2Brv Tg(Tnfsf13b)1Fma	MGI:3841109
cx4	Nfkb2^tm2Brv/Nfkb2^tm2Brv Traf3^tm1Bal/Traf3^tm1Bal	involves: 129S1/Sv * 129S4/SvJae * C57BL/6	MGI:4352677
cx5	Nfkb2^tm2Brv/Nfkb2^+ Traf3^tm1Bal/Traf3^tm1Bal	involves: 129S1/Sv * 129S4/SvJae * C57BL/6	MGI:4352678

Genotype
MGI:5441220

hm1

• Allelic Composition: Nfkb2^tm2Brv/Nfkb2^tm2Brv
• Genetic Background: involves: 129S1/Sv

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

hematopoietic system

abnormal gamma-delta T cell morphology ( J:169863 )

• reduced IL17-expressing splenic gamma-delta T cells and Vgamma4 gamma-delta T cells

decreased gamma-delta T cell number ( J:169863 )

• in the gut

immune system

abnormal gamma-delta T cell morphology ( J:169863 )

• reduced IL17-expressing splenic gamma-delta T cells and Vgamma4 gamma-delta T cells

decreased gamma-delta T cell number ( J:169863 )

• in the gut

Genotype
MGI:4352675

hm2

• Allelic Composition: Nfkb2^tm2Brv/Nfkb2^tm2Brv
• Genetic Background: involves: 129S1/Sv * C57BL/6

immune system

increased splenocyte apoptosis ( J:76380 )

• more cells in the white pulp undergo apoptosis than in wild-type mice

• however, stimulated B cells in the spleen exhibit normal levels of apoptosis

decreased B cell proliferation ( J:76380 )

• in LPS, anti-IgD-dextran, and anti-CD40 treated cells in the presence of IL4 and IL5

decreased B cell number ( J:76380 )

• 50% to 80% in the spleen as early as 1 week after birth

• the number of B cells in the bone marrow declines 50% between 8 and 12 weeks unlike in wild-type mice

• however, both mature and immature B cells are detected

increased CD4-positive, alpha-beta T cell number ( J:76380 )

increased CD8-positive, alpha-beta T cell number ( J:76380 )

abnormal spleen morphology ( J:76380 )

• spleen architecture is disrupted with diffuse, irregular B cell areas and absent perifollicular marginal zone and germinal centers unlike in wild-type mice

• sheep red blood cell-imminized mice exhibit very few germinal center cells and diffuse perifollicular staining of cells expressing surface IgD unlike in similarly treated wild-type mice

abnormal metallophilic macrophage morphology ( J:76380 )

• sheep red blood cell-imminized mice exhibit reduced numbers of metallophillic macrophages scattered throughout the white matter unlike in similarly treated wild-type mice

absent spleen germinal center ( J:76380 )

• in mice immunized with a variety of antigens, including sheep red blood cells and NP-KLH

absent spleen marginal zone ( J:76380 )

decreased IgA level ( J:76380 )

• 2-fold in naive cell

decreased IgG1 level ( J:76380 )

• following immunization with NP-KLH, mice exhibit a 4-fold and 10-fold reduction at days 7 and 10, respectively, in NP-specific isotype IgG1 compared to in similarly treated wild-type mice

increased IgG2a level ( J:76380 )

• 2.5-fold in naive cells

decreased IgG3 level ( J:76380 )

• in naive cells, IgG3 is reduced 3-fold compared to in wild-type mice

• following immunization with NP-LPS, mice exhibit a 10-fold and 30-fold reduction at days 7 and 21, respectively, in NP-specific IgG3 compared to in similarly treated wild-type mice

increased IgM level ( J:76380 )

• 4.5-fold in naive cells and 2 times higher in response to distinct stimuli compared to in wild-type mice

abnormal lymph node morphology ( J:76380 )

• lymph nodes exhibit similar morphological abnormalities as those observed in the spleen

absent lymph node germinal center ( J:76380 )

hematopoietic system

increased splenocyte apoptosis ( J:76380 )

• more cells in the white pulp undergo apoptosis than in wild-type mice

• however, stimulated B cells in the spleen exhibit normal levels of apoptosis

decreased B cell proliferation ( J:76380 )

• in LPS, anti-IgD-dextran, and anti-CD40 treated cells in the presence of IL4 and IL5

decreased B cell number ( J:76380 )

• 50% to 80% in the spleen as early as 1 week after birth

• the number of B cells in the bone marrow declines 50% between 8 and 12 weeks unlike in wild-type mice

• however, both mature and immature B cells are detected

increased CD4-positive, alpha-beta T cell number ( J:76380 )

increased CD8-positive, alpha-beta T cell number ( J:76380 )

abnormal spleen morphology ( J:76380 )

• spleen architecture is disrupted with diffuse, irregular B cell areas and absent perifollicular marginal zone and germinal centers unlike in wild-type mice

• sheep red blood cell-imminized mice exhibit very few germinal center cells and diffuse perifollicular staining of cells expressing surface IgD unlike in similarly treated wild-type mice

abnormal metallophilic macrophage morphology ( J:76380 )

• sheep red blood cell-imminized mice exhibit reduced numbers of metallophillic macrophages scattered throughout the white matter unlike in similarly treated wild-type mice

absent spleen germinal center ( J:76380 )

• in mice immunized with a variety of antigens, including sheep red blood cells and NP-KLH

absent spleen marginal zone ( J:76380 )

decreased IgA level ( J:76380 )

• 2-fold in naive cell

decreased IgG1 level ( J:76380 )

• following immunization with NP-KLH, mice exhibit a 4-fold and 10-fold reduction at days 7 and 10, respectively, in NP-specific isotype IgG1 compared to in similarly treated wild-type mice

increased IgG2a level ( J:76380 )

• 2.5-fold in naive cells

decreased IgG3 level ( J:76380 )

• in naive cells, IgG3 is reduced 3-fold compared to in wild-type mice

• following immunization with NP-LPS, mice exhibit a 10-fold and 30-fold reduction at days 7 and 21, respectively, in NP-specific IgG3 compared to in similarly treated wild-type mice

increased IgM level ( J:76380 )

• 4.5-fold in naive cells and 2 times higher in response to distinct stimuli compared to in wild-type mice

cellular

increased splenocyte apoptosis ( J:76380 )

• more cells in the white pulp undergo apoptosis than in wild-type mice

• however, stimulated B cells in the spleen exhibit normal levels of apoptosis

decreased B cell proliferation ( J:76380 )

• in LPS, anti-IgD-dextran, and anti-CD40 treated cells in the presence of IL4 and IL5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
common variable immunodeficiency		DOID:12177	OMIM:PS607594	J:206674

Genotype
MGI:3841109

cx3

• Allelic Composition: Nfkb2^tm2Brv/Nfkb2^tm2Brv; Tg(Tnfsf13b)1Fma/?
• Genetic Background: B6.Cg-Nfkb2^tm2Brv Tg(Tnfsf13b)1Fma

immune system

immune system phenotype ( J:113556 )

N • there are no elevated levels of anti-dsDNA antibodies detected in circulation compared to transgenic mice on a wild-type background that have high levels of auto-antbodies

decreased marginal zone B cell number ( J:113556 )

• marginal zone B cells are almost completely absent in the spleen

absent spleen marginal zone ( J:113556 )

• marginal zones are absent in these mice

abnormal B cell activation ( J:113556 )

• B cells have a strong response to T cell independent antigens producing higher levels of antigen-specific IgM, IgG2a, IgG2b class antibodies than wild-type controls

• however, there is no significant elevation of antigen-specific IgG1, IgG3, and IgA antibodies as is observed in transgenic mice on a wild-type background

• levels of antibodies produced are also lower than those in transgenic mice on a wild-type background

homeostasis/metabolism

increased urine protein level ( J:113556 )

• about half of 8-month old mice have proteinuria in their urine at 30 mg/dl concentration

renal/urinary system

increased urine protein level ( J:113556 )

• about half of 8-month old mice have proteinuria in their urine at 30 mg/dl concentration

hematopoietic system

decreased marginal zone B cell number ( J:113556 )

• marginal zone B cells are almost completely absent in the spleen

absent spleen marginal zone ( J:113556 )

• marginal zones are absent in these mice

abnormal B cell activation ( J:113556 )

• B cells have a strong response to T cell independent antigens producing higher levels of antigen-specific IgM, IgG2a, IgG2b class antibodies than wild-type controls

• however, there is no significant elevation of antigen-specific IgG1, IgG3, and IgA antibodies as is observed in transgenic mice on a wild-type background

• levels of antibodies produced are also lower than those in transgenic mice on a wild-type background

Genotype
MGI:4352677

cx4

• Allelic Composition: Nfkb2^tm2Brv/Nfkb2^tm2Brv; Traf3^tm1Bal/Traf3^tm1Bal
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * C57BL/6

mortality/aging

mortality/aging ( J:124635 )

N • unlike Traf3^tm1Bal homozygotes, mice survive into adulthood

immune system

immune system phenotype ( J:124635 )

N • mice do not exhibit the immune defects observed in single homozygotes

Genotype
MGI:4352678

cx5

• Allelic Composition: Nfkb2^tm2Brv/Nfkb2⁺; Traf3^tm1Bal/Traf3^tm1Bal
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * C57BL/6

mortality/aging

postnatal lethality, complete penetrance ( J:124635 )

• unlike Traf3^tm1Bal homozygotes, mice survive until 18 days