Phenotypes associated with this allele

• Allele Symbol: Mir146^tm1.1Bal
• Allele Name: targeted mutation 1.1, David Baltimore
• Allele ID: MGI:4882045
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mir146^tm1.1Bal/Mir146^tm1.1Bal	involves: C57BL/6	MGI:4887823
hm2	Mir146^tm1.1Bal/Mir146^tm1.1Bal	involves: C57BL/6 * FVB/N	MGI:5051638
cx3	Mir146^tm1.1Bal/Mir146^tm1.1Bal Tifab^tm1.1Dsta/Tifab^tm1.1Dsta	involves: 129 * C57BL/6 * C57BL/6J	MGI:5911667
cx4	Mir146^tm1.1Bal/Mir146^tm1.1Bal Nfkb1^tm1Bal/Nfkb1^tm1Bal	involves: 129P2/OlaHsd * C57BL/6	MGI:5317801
cx5	Foxp3^tm1.1Ayr/Foxp3^tm1.1Ayr Mir146^tm1.1Bal/Mir146^tm1.1Bal	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:4887824

Genotype
MGI:4887823

hm1

• Allelic Composition: Mir146^tm1.1Bal/Mir146^tm1.1Bal
• Genetic Background: involves: C57BL/6

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

mortality/aging

premature death ( J:173230 )

• mice become moribund by 18 to 22 months of age

hematopoietic system

enlarged spleen ( J:173230 )

• progressive starting at 5 to 6 months of age

• 6 to 7 times on necropsy

increased spleen weight ( J:173230 )

abnormal lymphopoiesis ( J:167922 )

• at 6 months, mice develop lympho- and myeloproliferative syndrome compared with wild-type mice

• however, mice exhibit normal lymphoid cell numbers at 6 to 8 weeks and disease is not present in mice treated with an IFNgamma blocker

myeloid hyperplasia ( J:167922 , J:173230 )

• at 6 months, mice develop lympho- and myeloproliferative syndrome compared with wild-type mice (J:167922)

• however, mice exhibit normal myeloid cell numbers at 6 to 8 weeks and disease is not present in mice treated with an IFNgamma blocker (J:167922)

• chronic myeloproliferation and myelofibrosis in the bone marrow (J:173230)

extramedullary hematopoiesis ( J:173230 )

• in the spleen

anemia ( J:173230 )

abnormal bone marrow cell morphology/development ( J:173230 )

• by 18 to 22 months, mice develop end-stage fibrosis or a hypercellular bone marrow and pale bone marrow unlike wild-type mice

increased bone marrow cell number ( J:173230 )

• by 18 to 22 months

decreased erythrocyte cell number ( J:173230 )

decreased hematocrit ( J:173230 )

decreased hemoglobin content ( J:173230 )

thrombocytopenia ( J:173230 )

increased regulatory T cell number ( J:167922 )

• in the periphery but not thymus

• not rescued by treatment with an IFNgamma blocker

decreased leukocyte cell number ( J:173230 )

decreased lymphocyte cell number ( J:173230 )

decreased monocyte cell number ( J:173230 )

abnormal regulatory T cell physiology ( J:167922 )

• increased proliferation of T regulatory cells

• impaired suppressive T regulatory cell function (measured by Th1 cytokine production)

immune system

enlarged spleen ( J:173230 )

• progressive starting at 5 to 6 months of age

• 6 to 7 times on necropsy

increased spleen weight ( J:173230 )

abnormal lymphopoiesis ( J:167922 )

• at 6 months, mice develop lympho- and myeloproliferative syndrome compared with wild-type mice

• however, mice exhibit normal lymphoid cell numbers at 6 to 8 weeks and disease is not present in mice treated with an IFNgamma blocker

myeloid hyperplasia ( J:167922 , J:173230 )

• at 6 months, mice develop lympho- and myeloproliferative syndrome compared with wild-type mice (J:167922)

• however, mice exhibit normal myeloid cell numbers at 6 to 8 weeks and disease is not present in mice treated with an IFNgamma blocker (J:167922)

• chronic myeloproliferation and myelofibrosis in the bone marrow (J:173230)

increased regulatory T cell number ( J:167922 )

• in the periphery but not thymus

• not rescued by treatment with an IFNgamma blocker

decreased leukocyte cell number ( J:173230 )

decreased lymphocyte cell number ( J:173230 )

decreased monocyte cell number ( J:173230 )

abnormal regulatory T cell physiology ( J:167922 )

• increased proliferation of T regulatory cells

• impaired suppressive T regulatory cell function (measured by Th1 cytokine production)

decreased interferon-gamma secretion ( J:167922 )

• from T cells upon activation under nonpolarizing Th0 conditions

neoplasm

increased T cell derived lymphoma incidence ( J:173230 )

• some mice develop lymphomas of B cell or mixed T and B cell lineage in the cervical lymph node, gastrointestinal tract, liver and kidney

increased B cell derived lymphoma incidence ( J:173230 )

• some mice develop lymphomas of B cell or mixed T and B cell lineage in the cervical lymph node, gastrointestinal tract, liver and kidney

• some mice develop high-grade diffuse large B cell lymphoma with apoptotic bodies and atypical mitosis

increased follicular lymphoma incidence ( J:173230 )

• low-grade in some mice

increased myeloid sarcoma incidence ( J:173230 )

• in the spleen and occasionally in the liver and kidney

• myeloid tumors are transplantable into immunocompromised mice

increased spleen neoplasm incidence ( J:173230 )

• spleen tumors with myeloid sarcoma histology in many mice

skeleton

myelofibrosis ( J:173230 )

• myelofibrosis in the bone marrow

growth/size/body

enlarged spleen ( J:173230 )

• progressive starting at 5 to 6 months of age

• 6 to 7 times on necropsy

increased spleen weight ( J:173230 )

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:173230 )

• some mice develop lymphomas of B cell or mixed T and B cell lineage in the cervical lymph node, gastrointestinal tract, liver and kidney

Genotype
MGI:5051638

hm2

• Allelic Composition: Mir146^tm1.1Bal/Mir146^tm1.1Bal
• Genetic Background: involves: C57BL/6 * FVB/N

Enlarged spleen and lymph nodes and multiorgan inflammation in Mir146^tm1.1Bal/Mir146^tm1.1Bal and Mir146^tm2.1Bal/Mir146^tm2.1Bal mice

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:173671 )

• in LPS-treated mice

premature death ( J:173671 )

• Background Sensitivity: aged mice on a C57BL/6 background lacking 129 exhibit less premature death than mice on a 129 and C57BL/6 background

immune system

myeloid hyperplasia ( J:173671 )

• massive

abnormal immune system physiology ( J:173671 )

• Background Sensitivity: aged mice on a C57BL/6 background lacking 129 exhibit delayed onset of immunoproliferative and autoimmune phenotype compared with mice on a 129 and C57BL/6 background

• penetrance of autoimmune phenotype is incomplete

abnormal T cell activation ( J:173671 )

• mice exhibit increased peripheral T cell activation compared with wild-type mice

abnormal macrophage physiology ( J:173671 )

• bone marrow-derived macrophage (BMDM) exhibit increased proliferation compared with wild-type cells

• however, inhibition of CSF1R activity rescues BMDM proliferation

increased macrophage nitric oxide production ( J:173671 )

• in response to LPS treatment

increased circulating interleukin-1 beta level ( J:173671 )

• in LPS-treated mice

increased circulating interleukin-10 level ( J:173671 )

• in LPS-treated mice

increased circulating interleukin-6 level ( J:173671 )

• in LPS-treated mice

increased circulating tumor necrosis factor level ( J:173671 )

• in LPS-treated mice

increased interleukin-1 beta secretion ( J:173671 )

• in LPS-treated bone marrow-derived macrophage

increased interleukin-6 secretion ( J:173671 )

• in LPS-treated bone marrow-derived macrophage

increased tumor necrosis factor secretion ( J:173671 )

• in LPS-treated bone marrow-derived macrophage

abnormal immune tolerance ( J:173671 )

• mice exhibit a loss of peripheral T cell tolerance compared with wild-type mice

increased susceptibility to endotoxin shock ( J:173671 )

• LPS-treated mice exhibit increased serum TNFalpha, IL6, IL1b, and IL10 serum levels, increased bone marrow derived macrophage production of TNFalpha, IL1b, and IL6, hypercytokinemia, and increased lethality compared with similarly treated wild-type mice

increased susceptibility to bacterial infection induced morbidity/mortality ( J:173671 )

• in LPS-treated mice

homeostasis/metabolism

increased macrophage nitric oxide production ( J:173671 )

• in response to LPS treatment

increased circulating interleukin-1 beta level ( J:173671 )

• in LPS-treated mice

increased circulating interleukin-10 level ( J:173671 )

• in LPS-treated mice

increased circulating interleukin-6 level ( J:173671 )

• in LPS-treated mice

increased circulating tumor necrosis factor level ( J:173671 )

• in LPS-treated mice

hematopoietic system

myeloid hyperplasia ( J:173671 )

• massive

abnormal T cell activation ( J:173671 )

• mice exhibit increased peripheral T cell activation compared with wild-type mice

abnormal macrophage physiology ( J:173671 )

• bone marrow-derived macrophage (BMDM) exhibit increased proliferation compared with wild-type cells

• however, inhibition of CSF1R activity rescues BMDM proliferation

increased macrophage nitric oxide production ( J:173671 )

• in response to LPS treatment

Genotype
MGI:5911667

cx3

• Allelic Composition: Mir146^tm1.1Bal/Mir146^tm1.1Bal; Tifab^tm1.1Dsta/Tifab^tm1.1Dsta
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J

hematopoietic system

decreased neutrophil cell number ( J:229024 )

• decrease in neutrophil numbers at 4 months post transplantation when bone marrow is transferred to lethally radiate syngenic recipient mice

• decrease is greater than in either single homozygote

decreased lymphocyte cell number ( J:229024 )

• decrease in lymphocyte numbers at 4 months post transplantation when bone marrow is transferred to lethally radiate syngenic recipient mice

• decrease is greater than in either single homozygote

abnormal hematopoietic stem cell morphology ( J:229024 )

• total colony formation is increased in vitro and progenitors show an additive increase in CFU-G colony formation compared to either single homozygote

immune system

decreased neutrophil cell number ( J:229024 )

• decrease in neutrophil numbers at 4 months post transplantation when bone marrow is transferred to lethally radiate syngenic recipient mice

• decrease is greater than in either single homozygote

decreased lymphocyte cell number ( J:229024 )

• decrease in lymphocyte numbers at 4 months post transplantation when bone marrow is transferred to lethally radiate syngenic recipient mice

• decrease is greater than in either single homozygote

Genotype
MGI:5317801

cx4

• Allelic Composition: Mir146^tm1.1Bal/Mir146^tm1.1Bal; Nfkb1^tm1Bal/Nfkb1^tm1Bal
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

hematopoietic system

hematopoietic system phenotype ( J:173230 )

N • myeloproliferation and splenomegaly observed in Mir146^tm1.1Bal knock-outs are rescued

Genotype
MGI:4887824

cx5

• Allelic Composition: Foxp3^tm1.1Ayr/Foxp3^tm1.1Ayr; Mir146^tm1.1Bal/Mir146^tm1.1Bal
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

premature aging ( J:167922 )

♀ • soon after 5 weeks when bone marrow is used to reconstitute wild-type mice

immune system

increased regulatory T cell number ( J:167922 )

♀ • when bone marrow is used to reconstitute wild-type mice

abnormal lymphocyte physiology ( J:167922 )

♀ • 6-7 weeks after transfer, massive lymphocyte activation and tissue infiltration in the lung, liver, and skin is observed when bone marrow is used to reconstitute wild-type mice

decreased interferon-gamma secretion ( J:167922 )

♀ • in T cells when bone marrow is used to reconstitute wild-type mice

blepharitis ( J:167922 )

♀ • as early as 5 weeks when bone marrow is used to reconstitute wild-type mice

conjunctivitis ( J:167922 )

♀ • as early as 5 weeks when bone marrow is used to reconstitute wild-type mice

dermatitis ( J:167922 )

♀ • as early as 5 weeks when bone marrow is used to reconstitute wild-type mice

integument

dermatitis ( J:167922 )

♀ • as early as 5 weeks when bone marrow is used to reconstitute wild-type mice

vision/eye

blepharitis ( J:167922 )

♀ • as early as 5 weeks when bone marrow is used to reconstitute wild-type mice

conjunctivitis ( J:167922 )

♀ • as early as 5 weeks when bone marrow is used to reconstitute wild-type mice

hematopoietic system

increased regulatory T cell number ( J:167922 )

♀ • when bone marrow is used to reconstitute wild-type mice

abnormal lymphocyte physiology ( J:167922 )

♀ • 6-7 weeks after transfer, massive lymphocyte activation and tissue infiltration in the lung, liver, and skin is observed when bone marrow is used to reconstitute wild-type mice