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)
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support.	last database update 04/09/2024 MGI 6.23