All Phenotypes Ifnar1<tm1Pjh> MGI Mouse

increased susceptibility to Picornaviridae infection induced morbidity/mortality ( J:36004 )

• following i.p. injection of EMCV at 10 times the TCID₅₀, all neonatal homozygotes died suddenly within 38 hrs of inoculation, whereas all control mice had a mean survival time of ~60 hrs

increased susceptibility to Togaviridae infection induced morbidity/mortality ( J:36004 )

• following i.p. injection of SFV at 100X the TCID₅₀ on L cells, all neonatal homozygotes became moribund at 21 hrs after inoculation and died 3 hrs later, whereas wild-type and heterozygous controls showed a mean survival time of ~72 hrs

increased leukocyte cell number ( J:36004 )

• homozygotes display increased levels of myeloid lineage cells in peripheral blood and bone marrow, as revealed by staining with Mac-1 and Gr-1 antibodies

abnormal macrophage physiology ( J:36004 )

• in response to graded low doses (80-625 ug/ml) of CSF-1, mutant bone marrow-derived macrophages (BMDMs) showed a significantly lower dose-dependent increase in thymidine incorporation than similarly-treated wild-type BMDMs; however, mutant BMDMs displayed a nearly normal proliferation in response to 5000 ug/ml of CSF-1

• mutant BMDMs were resistant to the antiproliferative effects of IFN-alpha (12.5-400 units/ml), whereas wild-type cells were inhibited by 95% in response to 12.5 units/ml and by 99% in response to higher IFN-alpha levels

• unlike wild-type BMDMs where LPS strongly inhibited CSF-1-stimulated thymidine incorporation, mutant BMDMs were resistant to the antiproliferative effects of LPS (100 ng/ml)

increased susceptibility to Picornaviridae infection ( J:36004 )

• in vitro, primary MEFs derived from E13 homozygous mutant embryos failed to exhibit protection against encephalomyocarditis virus (EMCV) infection by high levels of IFN-alpha or IFN-beta (>3000 units/ml), whereas wild-type MEFs were protected by levels as low as 3-58 units/ml

increased susceptibility to Picornaviridae infection induced morbidity/mortality ( J:36004 )

• following i.p. injection of EMCV at 10 times the TCID₅₀, all neonatal homozygotes died suddenly within 38 hrs of inoculation, whereas all control mice had a mean survival time of ~60 hrs

increased susceptibility to Togaviridae infection ( J:36004 )

• 24 hrs following i.p. injection of Semliki Forest virus (SFV at 100X the tissue culture 50% infective dose (TCID₅₀) on L cells), viral titers of 10⁴ to 10¹⁰ were detected in the lung, spleen, brain, liver and kidney of homozygous mutant mice, whereas no virus was detected in the organs of wild-type and heterozygous controls

• in vitro, primary MEFs derived from E13 homozygous mutant embryos failed to exhibit protection against SFV infection by high levels of IFN-alpha or IFN-beta (>3000 units/ml), whereas wild-type MEFs were protected by levels as low as 3-58 units/ml

• mutant BMDMs failed to develop an antiviral response to as high as 10,000 units/ml of IFN-alpha, whereas wild-type BMDMs showed a response to as little as 1 unit/ml of IFN-alpha

• in contrast, a similar IFN-gamma activity (~3 units/ml) was required to attain 50% inhibition of SFV-induced cytopathic effect in wild-type and mutant BMDMs

increased susceptibility to Togaviridae infection induced morbidity/mortality ( J:36004 )

• following i.p. injection of SFV at 100X the TCID₅₀ on L cells, all neonatal homozygotes became moribund at 21 hrs after inoculation and died 3 hrs later, whereas wild-type and heterozygous controls showed a mean survival time of ~72 hrs

increased leukocyte cell number ( J:36004 )

• homozygotes display increased levels of myeloid lineage cells in peripheral blood and bone marrow, as revealed by staining with Mac-1 and Gr-1 antibodies

abnormal macrophage physiology ( J:36004 )

• in response to graded low doses (80-625 ug/ml) of CSF-1, mutant bone marrow-derived macrophages (BMDMs) showed a significantly lower dose-dependent increase in thymidine incorporation than similarly-treated wild-type BMDMs; however, mutant BMDMs displayed a nearly normal proliferation in response to 5000 ug/ml of CSF-1

• mutant BMDMs were resistant to the antiproliferative effects of IFN-alpha (12.5-400 units/ml), whereas wild-type cells were inhibited by 95% in response to 12.5 units/ml and by 99% in response to higher IFN-alpha levels

• unlike wild-type BMDMs where LPS strongly inhibited CSF-1-stimulated thymidine incorporation, mutant BMDMs were resistant to the antiproliferative effects of LPS (100 ng/ml)

abnormal enzyme/coenzyme activity ( J:36004 )

• basal levels of 2'-5' oligoadenylate synthetase (2'-5'OAS) activity in primary MEFs derived from E13 homozygous mutant embryos were severely reduced relative to those in wild-type and heterozygous MEFs (23 +/- 9 vs 189 +/- 54 and 130 +/- 64 pmol/ug of protein, respectively)

• unlike in wild-type MEFs, treatment with IFN-alpha or IFN-beta failed to induce 2'-5'OAS activity in homozygous mutant MEFs, indicating no signal transduction in response to type I IFNs

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

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

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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