Phenotypes associated with this allele

• Allele Symbol: Nfkb1^tm1Brv
• Allele Name: targeted mutation 1, Rodrigo Bravo
• Allele ID: MGI:2179707
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nfkb1^tm1Brv/Nfkb1^tm1Brv	involves: 129S1/Sv	MGI:3768242
hm2	Nfkb1^tm1Brv/Nfkb1^tm1Brv	involves: 129S1/Sv * C57BL/6	MGI:3852530
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:3768242

hm1

• Allelic Composition: Nfkb1^tm1Brv/Nfkb1^tm1Brv
• Genetic Background: involves: 129S1/Sv

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

mortality/aging

premature death ( J:46912 )

• mice begin to die after 2 months and survival at 100 days is 50% whereas almost all wild-type mice are alive at day 100

preweaning lethality, incomplete penetrance ( J:46912 )

• 20% of mice die prior to weaning

immune system

myeloid hyperplasia ( J:46912 )

• mice exhibit myeloid hyperplasia in the bone marrow associated with decreased erythrocyte cell number

decreased single-positive T cell number ( J:46912 )

• single positive CD4+ or CD8+ T cells are decreased in the spleen and lymph node

• the number of Thy 1.2+ cells is decreased by 50% compared to wild-type in the peripheral T cell population

abnormal lymphocyte physiology ( J:46912 )

increased B cell proliferation ( J:46912 )

• at low levels of stimulation, B cell proliferation is increased 4- to 5-foldcompared to in wild-type mice

decreased T cell proliferation ( J:46912 )

• T cell proliferation stimulated by anti-CD3 or anti-CD3 and anti-CD28 antibodies do not proliferate as well as wild-type T cells

• however, proliferation stimulated by PMA and PHA is normal

decreased IgG3 level ( J:46912 )

• IgG3 levels are decreased 4-fold

increased immunoglobulin level ( J:46912 )

• serum Ig levels are increased 5-fold

increased IgE level ( J:46912 )

• IgE levels are increased 50-fold

increased IgG1 level ( J:46912 )

• IgG1 levels are increased 18-fold

abnormal lymph organ size ( J:46912 )

enlarged spleen ( J:46912 )

• mice develop spleen enlargement due to extramedullary hematopoiesis and follicular expansion with loss of mantle and marginal zone differentiation at 3 weeks of age that worsens with age

enlarged lymph nodes ( J:46912 )

• mice develop lymph node enlargement at 3 weeks that worsens with age

• however, lymphoid cell numbers are not increased

abnormal humoral immune response ( J:46912 )

• after 2 and 3 weeks stimulated with NP-KLH, IgG1 production is increased 2- to 3-fold compared to in wild-type mice

• after 3 weeks of stimulation with LPS, IgG3 levels are reduced 3-fold

• however, basal and specific antibody production is not seriously affected

abnormal cytokine secretion ( J:46912 )

• stimulated and non-stimulated macrophages produce less cytokines that wild-type cells (17- to 86-fold reduction in unstimulated cells and 2- to 8-fold reduction in stimulated cells)

decreased interleukin-2 secretion ( J:46912 )

• stimulated T cells produce 3- to 6-fold less IL-2 than wild-type

decreased interleukin-4 secretion ( J:46912 )

• stimulated T cells produce 3- to 6-fold less IL-4 than wild-type

decreased tumor necrosis factor secretion ( J:46912 )

• stimulated T cells produce 3- to 6-fold less TNF-alpha than wild-type

abnormal inflammatory response ( J:46912 )

liver inflammation ( J:46912 )

• mild to moderate perivascular and periportal mixed infiltration of inflammatory cells is mainly composed of lymphocytic cells

lung inflammation ( J:46912 )

• mild to moderate perivascular and periairway mixed infiltration of inflammatory cells is mainly composed of lymphocytic cells

increased susceptibility to bacterial infection ( J:46912 )

• mice in conventional housing develop eye and/or nasal infections produced by Staphylococcus xylosis and Pasteurella haemolytica unlike wild-type mice

• however, mice housed in microinsolators do not develop infections

growth/size/body

postnatal growth retardation ( J:46912 )

• after weaning mice exhibit growth retardation

enlarged spleen ( J:46912 )

• mice develop spleen enlargement due to extramedullary hematopoiesis and follicular expansion with loss of mantle and marginal zone differentiation at 3 weeks of age that worsens with age

behavior/neurological

lethargy ( J:46912 )

• after weaning surviving mice appear sick, have rough coats and are lethargic

hematopoietic system

enlarged spleen ( J:46912 )

• mice develop spleen enlargement due to extramedullary hematopoiesis and follicular expansion with loss of mantle and marginal zone differentiation at 3 weeks of age that worsens with age

myeloid hyperplasia ( J:46912 )

• mice exhibit myeloid hyperplasia in the bone marrow associated with decreased erythrocyte cell number

extramedullary hematopoiesis ( J:46912 )

• extramedullary hematopoiesis results in splenomegaly at 3 weeks and worsens with age

• erythroblasts accumulate in the spleen

abnormal bone marrow cell morphology/development ( J:46912 )

• erythroblasts are decreased in the bone marrow whereas granulocytes are slightly increased

decreased erythrocyte cell number ( J:46912 )

• decreased erythrocyte cell numbers are associated with myeloid hyperplasia in the bone marrow

decreased single-positive T cell number ( J:46912 )

• single positive CD4+ or CD8+ T cells are decreased in the spleen and lymph node

• the number of Thy 1.2+ cells is decreased by 50% compared to wild-type in the peripheral T cell population

abnormal lymphocyte physiology ( J:46912 )

increased B cell proliferation ( J:46912 )

• at low levels of stimulation, B cell proliferation is increased 4- to 5-foldcompared to in wild-type mice

decreased T cell proliferation ( J:46912 )

• T cell proliferation stimulated by anti-CD3 or anti-CD3 and anti-CD28 antibodies do not proliferate as well as wild-type T cells

• however, proliferation stimulated by PMA and PHA is normal

decreased IgG3 level ( J:46912 )

• IgG3 levels are decreased 4-fold

increased immunoglobulin level ( J:46912 )

• serum Ig levels are increased 5-fold

increased IgE level ( J:46912 )

• IgE levels are increased 50-fold

increased IgG1 level ( J:46912 )

• IgG1 levels are increased 18-fold

liver/biliary system

liver inflammation ( J:46912 )

• mild to moderate perivascular and periportal mixed infiltration of inflammatory cells is mainly composed of lymphocytic cells

respiratory system

lung inflammation ( J:46912 )

• mild to moderate perivascular and periairway mixed infiltration of inflammatory cells is mainly composed of lymphocytic cells

integument

rough coat ( J:46912 )

• after weaning surviving mice appear sick, have rough coats and are lethargic

cellular

increased B cell proliferation ( J:46912 )

• at low levels of stimulation, B cell proliferation is increased 4- to 5-foldcompared to in wild-type mice

decreased T cell proliferation ( J:46912 )

• T cell proliferation stimulated by anti-CD3 or anti-CD3 and anti-CD28 antibodies do not proliferate as well as wild-type T cells

• however, proliferation stimulated by PMA and PHA is normal

Genotype
MGI:3852530

hm2

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

skeleton

skeleton phenotype ( J:44112 )

N • mice exhibit normal bone structure

decreased osteoclast cell number ( J:44112 )

immune system

decreased osteoclast cell number ( J:44112 )

hematopoietic system

decreased osteoclast cell number ( J:44112 )

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