Phenotypes associated with this allele

• Allele Symbol: Mir146^tm2.1Bal
• Allele Name: targeted mutation 2.1, David Baltimore
• Allele ID: MGI:5049868
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mir146^tm2.1Bal/Mir146^tm2.1Bal	involves: 129S1/Sv * C57BL/6 * FVB/N	MGI:5051639

Genotype
MGI:5051639

hm1

• Allelic Composition: Mir146^tm2.1Bal/Mir146^tm2.1Bal
• Genetic Background: involves: 129S1/Sv * C57BL/6 * FVB/N

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

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 )

• at 6 to 8 months

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

• aged female mice exhibit accelerated premature death compared with male mice

immune system

immune system phenotype ( J:173671 )

N • mice exhibit normal numbers of T and B cells

enlarged spleen ( J:173671 )

• at 6 to 8 months

increased spleen weight ( J:173671 )

• in aged mice

myeloid hyperplasia ( J:173671 )

• massive

• at 9 to 12 months, some mice exhibit myeloproliferative disease unlike wild-type mice

decreased lymphocyte cell number ( J:173671 )

• in aged mice

decreased monocyte cell number ( J:173671 )

• in aged mice

abnormal spleen B cell follicle morphology ( J:173671 )

• young and 6 to 9 month old mice exhibit follicular hyperplasia in the spleen unlike in wild-type mice

increased spleen germinal center number ( J:173671 )

increased spleen germinal center size ( J:173671 )

enlarged lymph nodes ( J:173671 )

• at 6 to 8 months in some mice

abnormal immune system physiology ( J:173671 )

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

• 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

• moderate in aged 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 anti-double stranded DNA antibody level ( J:173671 )

• 60-fold in aged mice

increased acute inflammation ( J:173671 )

• at 6 to 8 months, mice exhibit lymphocytic and monocytic infiltration in various organs with some tissue damage 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

hematopoietic system

enlarged spleen ( J:173671 )

• at 6 to 8 months

increased spleen weight ( J:173671 )

• in aged mice

myeloid hyperplasia ( J:173671 )

• massive

• at 9 to 12 months, some mice exhibit myeloproliferative disease unlike wild-type mice

extramedullary hematopoiesis ( J:173671 )

• at 6 to 9 months in the spleen

• in aged mice

anemia ( J:173671 )

• in aged mice

decreased hematocrit ( J:173671 )

• in aged mice

decreased hemoglobin content ( J:173671 )

• in aged mice

thrombocytopenia ( J:173671 )

• in aged mice

decreased lymphocyte cell number ( J:173671 )

• in aged mice

decreased monocyte cell number ( J:173671 )

• in aged mice

abnormal spleen B cell follicle morphology ( J:173671 )

• young and 6 to 9 month old mice exhibit follicular hyperplasia in the spleen unlike in wild-type mice

increased spleen germinal center number ( J:173671 )

increased spleen germinal center size ( J:173671 )

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

abnormal bone marrow cell physiology ( J:173671 )

• at 6 to 9 months, some mice exhibit bone marrow failure unlike wild-type mice

neoplasm

increased tumor incidence ( J:173671 )

• aged mice develop frank tumors in their secondary lymphoid organs, frequently in the spleen

• 20% of aged mice exhibit neoplastic lesions compared with 2% of wild-type mice

increased hemolymphoid system tumor incidence ( J:173671 )

• after 12 months, some mice exhibit high-grade large cell hemato-lymphoid neoplasms unlike wild-type mice

increased follicular lymphoma incidence ( J:173671 )

• at 9 to 12 months, some mice exhibit low-grade follicular lymphoma unlike wild-type mice

• around 1 year of age, some mice exhibit high-grade follicular lymphoma unlike wild-type 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

• moderate in aged mice

increased circulating tumor necrosis factor level ( J:173671 )

• in LPS-treated mice

growth/size/body

enlarged spleen ( J:173671 )

• at 6 to 8 months

increased spleen weight ( J:173671 )

• in aged mice