Phenotypes associated with this allele

• Allele Symbol: Nfkb2^tm1Brv
• Allele Name: targeted mutation 1, Rodrigo Bravo
• Allele ID: MGI:2179689
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nfkb2^tm1Brv/Nfkb2^tm1Brv	involves: 129S1/Sv * C57BL/6	MGI:3852509
ht2	Nfkb2^tm1Brv/Nfkb2^+	involves: 129S1/Sv * C57BL/6	MGI:3852510
cx3	Nfkb1^tm1Brv/Nfkb1^tm1Brv Nfkb2^tm1Brv/Nfkb2^tm1Brv	involves: 129S1/Sv * C57BL/6	MGI:3852529
cx4	Nfkb1^tm1Brv/Nfkb1^tm1Brv Nfkb2^tm1Brv/Nfkb2^+	involves: 129S1/Sv * C57BL/6	MGI:3852531

Genotype
MGI:3852509

hm1

• Allelic Composition: Nfkb2^tm1Brv/Nfkb2^tm1Brv
• Genetic Background: involves: 129S1/Sv * C57BL/6

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

Stomach abnormalities in Nfkb2^tm1Brv/Nfkb2^tm1Brv mice

mortality/aging

premature death ( J:43469 )

immune system

increased B cell proliferation ( J:43469 )

• LPS-induced B cell proliferation is increased compared to in similarly treated wild-type mice

increased T cell proliferation ( J:43469 )

• T cell proliferation in response to anti-CD3, anti-CD3 plus anti-CD28, or PMA plus PHA is two- to six-fold more efficient than for similarly treated wild-type cells

abnormal thymus corticomedullary boundary morphology ( J:43469 )

• poorly demarcated

thymus atrophy ( J:43469 )

• at 3 weeks

increased granulocyte number ( J:43469 )

• in the bone marrow and peripheral blood

abnormal lymphocyte cell number ( J:43469 )

• the ratio of T to B cell is slightly decreased in the lymph node compared to in wild-type mice

• however, lymphocyte development is normal

abnormal T cell number ( J:43469 )

• the percentage of T cells in the spleen is decreased compared to in wild-type mice

decreased double-positive T cell number ( J:43469 )

• at P10, CD4+CD8+ double positive thymic cells are nearly absent

abnormal T cell subpopulation ratio ( J:43469 )

• double positive T cells are nearly absent and single positive T cells predominate

intermingled spleen red and white pulp ( J:43469 )

• at 3 weeks

decreased spleen weight ( J:43469 )

• starting at P10 to P14

spleen atrophy ( J:43469 )

• at 3 weeks

spleen hypoplasia ( J:43469 )

• at 3 weeks

abnormal lymph node cortex morphology ( J:43469 )

• after 2 weeks, the paracortical area is increased compared to in wild-type mice

abnormal lymph node B cell domain morphology ( J:43469 )

• mice exhibit reduced number and cell density of lymphatic follicles compared to in wild-type mice

enlarged lymph nodes ( J:43469 )

• after 2 weeks

abnormal cytokine secretion ( J:43469 )

• anti-CD3 and anti-CD28-stimulated production of cytokines IL2, IL4, IL10, GM-CSF (granulocyte monocyte colony stimulating factor), and TNF-alpha is increased 5- to 35-fold compared to in similarly treated wild-type cells

increased interleukin-10 secretion ( J:43469 )

• following anti-CD3 and anti-CD28 stimulation

increased interleukin-2 secretion ( J:43469 )

• following anti-CD3 and anti-CD28 stimulation

increased interleukin-4 secretion ( J:43469 )

• following anti-CD3 and anti-CD28 stimulation

increased tumor necrosis factor secretion ( J:43469 )

• following anti-CD3 and anti-CD28 stimulation

digestive/alimentary system

abnormal stomach cardiac region morphology ( J:43469 )

• mice exhibit hyperkeratosis in the cardiac portion of the stomach unlike in wild-type mice

• at 3 weeks, gastric abnormalities increase in severity until the gastric lumen is occluded unlike in wild-type mice

stomach epithelial hyperplasia ( J:43469 )

• in the antrum with lymphocytic infiltrate in the lamina propria

small stomach ( J:43469 )

• at 2 weeks

growth/size/body

decreased body size ( J:43469 )

• at P10 to P14

decreased body weight ( J:43469 )

• after P10 to P14, mice weight 25% to 30% less than wild-type mice

weight loss ( J:43469 )

• after P10 to P14

behavior/neurological

abnormal food intake ( J:43469 )

• at 2 weeks, stomach contains little food or milk unlike wild-type mice

hunched posture ( J:43469 )

• after P10 to P14

skeleton

abnormal bone marrow morphology ( J:43469 )

• at 3 weeks, the number of granulocytes is increased and a reduced number of other hematopoeitic cell populations compared to in wild-type mice

hematopoietic system

increased B cell proliferation ( J:43469 )

• LPS-induced B cell proliferation is increased compared to in similarly treated wild-type mice

increased T cell proliferation ( J:43469 )

• T cell proliferation in response to anti-CD3, anti-CD3 plus anti-CD28, or PMA plus PHA is two- to six-fold more efficient than for similarly treated wild-type cells

abnormal thymus corticomedullary boundary morphology ( J:43469 )

• poorly demarcated

thymus atrophy ( J:43469 )

• at 3 weeks

abnormal definitive hematopoiesis ( J:43469 )

• hematopoietic abnormalities increase in severity by 3 weeks

anemia ( J:43469 )

• in the liver and spleen at 3 weeks

increased granulocyte number ( J:43469 )

• in the bone marrow and peripheral blood

abnormal lymphocyte cell number ( J:43469 )

• the ratio of T to B cell is slightly decreased in the lymph node compared to in wild-type mice

• however, lymphocyte development is normal

abnormal T cell number ( J:43469 )

• the percentage of T cells in the spleen is decreased compared to in wild-type mice

decreased double-positive T cell number ( J:43469 )

• at P10, CD4+CD8+ double positive thymic cells are nearly absent

abnormal T cell subpopulation ratio ( J:43469 )

• double positive T cells are nearly absent and single positive T cells predominate

intermingled spleen red and white pulp ( J:43469 )

• at 3 weeks

decreased spleen weight ( J:43469 )

• starting at P10 to P14

spleen atrophy ( J:43469 )

• at 3 weeks

spleen hypoplasia ( J:43469 )

• at 3 weeks

integument

disheveled coat ( J:43469 )

• after P10 to P14

endocrine/exocrine glands

abnormal thymus corticomedullary boundary morphology ( J:43469 )

• poorly demarcated

thymus atrophy ( J:43469 )

• at 3 weeks

cellular

increased B cell proliferation ( J:43469 )

• LPS-induced B cell proliferation is increased compared to in similarly treated wild-type mice

increased T cell proliferation ( J:43469 )

• T cell proliferation in response to anti-CD3, anti-CD3 plus anti-CD28, or PMA plus PHA is two- to six-fold more efficient than for similarly treated wild-type cells

Genotype
MGI:3852510

ht2

• Allelic Composition: Nfkb2^tm1Brv/Nfkb2⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

digestive/alimentary system

stomach epithelial hyperplasia ( J:43469 )

• at 10 months, mice exhibit mild gastric hyperplasia compared to in wild-type mice

Genotype
MGI:3852529

cx3

• Allelic Composition: Nfkb1^tm1Brv/Nfkb1^tm1Brv; Nfkb2^tm1Brv/Nfkb2^tm1Brv
• Genetic Background: involves: 129S1/Sv * C57BL/6

skeleton

abnormal osteoclast differentiation ( J:44112 )

• fewer osteoclasts form while more bone-residing macrophages are detected compared to in wild-type mice

tooth impaction ( J:44112 )

• tooth eruption is prevented by a superficial bone plate on the mandible and maxilla and impacted teeth are poorly invested in the surrounding alveolar bone unlike in wild-type mice

• however, mice reconstituted with wild-type marrow exhibit only delayed tooth eruption

decreased osteoclast cell number ( J:44112 )

abnormal long bone morphology ( J:44112 )

• persistent cartilaginous and osseous trabecular are found throughout the epiphysis, metaphysis and diaphysis unlike in wild-type mice

• endochondral bones exhibit thin, hypocellular growth plates and wide, cavernous marrow spaces unlike in wild-type mice

abnormal long bone epiphyseal plate morphology ( J:44112 )

• the proliferating and hypertrophic zones are arranged in irregular clusters unlike the discrete columns observed in wild-type mice

abnormal bone marrow cavity morphology ( J:44112 )

• the bone marrow cavity is filled with unresorbed primary spongiosa that reduces the space 80% compared to in wild-type mice

osteopetrosis ( J:44112 )

immune system

abnormal osteoclast differentiation ( J:44112 )

• fewer osteoclasts form while more bone-residing macrophages are detected compared to in wild-type mice

decreased osteoclast cell number ( J:44112 )

increased macrophage cell number ( J:44112 )

• the number of bone-residing macrophages is increased compared to in wild-type mice

• the number of macrophages in the spleen, blood, and bone marrow is increased compared to in wild-type mice

abnormal cytokine secretion ( J:44112 )

• LPS and IFN-gamma-stimulated macrophages exhibit reduced IL6 and GM-CSF (granulocyte monocyte colony stimulating factor) production compared to similarly treated wild-type cell

decreased interleukin-6 secretion ( J:44112 )

• LPS and IFN-gamma-stimulated macrophages exhibit reduced IL6 production compared to similarly treated wild-type cell

growth/size/body

tooth impaction ( J:44112 )

• tooth eruption is prevented by a superficial bone plate on the mandible and maxilla and impacted teeth are poorly invested in the surrounding alveolar bone unlike in wild-type mice

• however, mice reconstituted with wild-type marrow exhibit only delayed tooth eruption

postnatal growth retardation ( J:44112 )

• after P10

craniofacial

abnormal craniofacial morphology ( J:44112 )

• after P10

tooth impaction ( J:44112 )

• tooth eruption is prevented by a superficial bone plate on the mandible and maxilla and impacted teeth are poorly invested in the surrounding alveolar bone unlike in wild-type mice

• however, mice reconstituted with wild-type marrow exhibit only delayed tooth eruption

hematopoietic system

abnormal osteoclast differentiation ( J:44112 )

• fewer osteoclasts form while more bone-residing macrophages are detected compared to in wild-type mice

decreased osteoclast cell number ( J:44112 )

increased macrophage cell number ( J:44112 )

• the number of bone-residing macrophages is increased compared to in wild-type mice

• the number of macrophages in the spleen, blood, and bone marrow is increased compared to in wild-type mice

cellular

abnormal osteoclast differentiation ( J:44112 )

• fewer osteoclasts form while more bone-residing macrophages are detected compared to in wild-type mice

Genotype
MGI:3852531

cx4

• Allelic Composition: Nfkb1^tm1Brv/Nfkb1^tm1Brv; Nfkb2^tm1Brv/Nfkb2⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

skeleton

abnormal bone structure ( J:44112 )

• mice exhibit only subtle changes in bone structure

abnormal osteoclast differentiation ( J:44112 )

• osteoclast differentiation is arrested before fusion

decreased osteoclast cell number ( J:44112 )

• no mature osteoclasts are detected in cultures of spleen cells unlike those of wild-type cell

immune system

abnormal osteoclast differentiation ( J:44112 )

• osteoclast differentiation is arrested before fusion

decreased osteoclast cell number ( J:44112 )

• no mature osteoclasts are detected in cultures of spleen cells unlike those of wild-type cell

hematopoietic system

abnormal osteoclast differentiation ( J:44112 )

• osteoclast differentiation is arrested before fusion

decreased osteoclast cell number ( J:44112 )

• no mature osteoclasts are detected in cultures of spleen cells unlike those of wild-type cell

cellular

abnormal osteoclast differentiation ( J:44112 )

• osteoclast differentiation is arrested before fusion