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Phenotypes Associated with This Genotype
Genotype
MGI:3577712
Allelic
Composition
Myd88tm1Aki/Myd88tm1Aki
Genetic
Background
B6.129P2-Myd88tm1Aki
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Myd88tm1Aki mutation (8 available); any Myd88 mutation (42 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
respiratory system
• rMA15 SARS-CoV-infected mice show denuding bronchiolitis not seen in wild-type mice

mortality/aging
• rMA15 SARS-CoV-infected mice show greater than 90% mortality by 6 dpi compared to 100% survival in controls

cellular
• 5 days after lung injury, mutants show significantly increased numbers of apoptotic lung epithelial and inflammatory cells
• dendritic cell maturation fails to occur in vivo upon exposure to TLR9 agonists
• improved differentiation of progenitor cells into neurons
• survival of newly formed neurons is reduced

homeostasis/metabolism
• knockout mice are more susceptible to bleomycin-induced lung injury
• moderately protected from ischemia reperfusion injury as measured by serum creatinine levels 24 hours after injury

immune system
• dendritic cell maturation fails to occur in vivo upon exposure to TLR9 agonists
• increased numbers of dendritic cells in brains of mice infected with Plasmodium
• response to LPS and CpG is completely abrogated
• induction of the antigen-specific CD8+ T-cell response by immunizing with soluble ovalbumin and TLR9 agonists, but not TLR2 and TLR6 agonists, was severely impaired
• cytokine secretion elicited by zymosan or LPS is impaired (J:116670)
• following infection with attenuated yellow fever vaccine 17D (YF-17D), dendritic cells produce less IL-12p40, IL-6 and interferon-gamma relative to wild-type mice (J:118954)
• LPS-induced cytokine production by BMDCs is almost abolished compared to controls and Myd88-sufficient mutants (J:116670)
• rMA15 SARS-CoV-infected mice show decreased expression of proinflammatory cytokines and chemokines, showing reduced induction of CCL2, CCL3, and CCL5, TNF-alpha, and IL-1beta (J:162707)
• hyaluronan fragment-induced expression of chemokines by peritoneal macrophages is completely abolished in double knockout mice
• CpG-A or RNA polyuridylic acid induced production of interferon-alpha was abolished in plasmacytoid dendritic cells
• less up regulation of INF-gamma in Plasmodium infection (J:116763)
• following infection with attenuated yellow fever vaccine 17D (YF-17D), dendritic cells produce less interferon-gamma (J:118954)
• after stimulation with zymosan, TNF production is significantly reduced in Myd88-deficient animals
• less upregulation of IL-12b in Plasmodium infection (J:116763)
• following infection with attenuated yellow fever vaccine 17D (YF-17D), dendritic cells produce less IL-12p40 relative to wild-type mice (J:118954)
• following infection with attenuated yellow fever vaccine 17D (YF-17D), dendritic cells produce less IL-6 relative to wild-type mice (J:118954)
• following treatment with PbA(Plasmodium bergbei ANKA)-parasitized erythrocytes or LPS-stimulation, IL-6 secretion is reduced (J:121070)
• after stimulation with zymosan, TNF production is significantly reduced in Myd88-deficient animals (J:116670)
• less upregulation of TNF-alpha in Plasmodium infection (J:116763)
• following treatment with PbA(Plasmodium bergbei ANKA)-parasitized erythrocytes or LPS-stimulation, TNF secretion is reduced (J:121070)
• in a model of induced pneumococcal meningitis-associated labyrinthitis, homozygotes exhibit a significantly lower granulocytic infiltration of the labyrinth and increased bacterial density in the cochlea at 24 hrs post-infection relative to wild-type control mice
• rMA15 SARS-CoV-infected mice show denuding bronchiolitis not seen in wild-type mice
• the innate immune response is severely delayed in rMA15 SARS-CoV-infected mice, with lung inflammation becoming evident at 6 dpi compared to 2 dpi in wild-type mice and delay of recruitment of inflammatory monocytes/macrophages to lungs
• NK cells fail to make IFN-gamma in response to injections of TLR9 agonists
• TNF production is impaired in thioglycollate-elicited macrophages treated with intact zymosan
• cytokine production by macrophages cultured with P. carinii cysts is reduced compared to wild-type
• following treatment with PbA (Plasmodium bergbei ANKA)-parasitized erythrocytes, mice have a decreased immune response in terms of TNF and IL-6 secretion and response to CpG
• resistant to cerebral malaria but eventually die of extremely high parasitemia
• mice show increased susceptibility to infection with a recombinant mouse-adapted SARS-CoV, rMA15 , showing enhanced pulmonary pathology, higher viral loads in lung tissue, and greater than 90% mortality by 6 days post infection (dpi)
• rMA15 SARS-CoV-infected mice show extensive lung pathology, exhibiting denuding bronchiolitis and peribronchivascular edema not seen in wild-type mice and more severe perivascular cuffing
• however, infectious virus is not detected in the brain, liver, or kidney and only sporadic viral titers are seen in the spleen
• rMA15 SARS-CoV-infected mice show greater than 90% mortality by 6 dpi compared to 100% survival in controls
• increased susceptibility to encephalomyocarditis virus (EMCV) infection compared to wildtype

hematopoietic system
• dendritic cell maturation fails to occur in vivo upon exposure to TLR9 agonists
• increased numbers of dendritic cells in brains of mice infected with Plasmodium
• NK cells fail to make IFN-gamma in response to injections of TLR9 agonists
• induction of the antigen-specific CD8+ T-cell response by immunizing with soluble ovalbumin and TLR9 agonists, but not TLR2 and TLR6 agonists, was severely impaired
• TNF production is impaired in thioglycollate-elicited macrophages treated with intact zymosan
• cytokine production by macrophages cultured with P. carinii cysts is reduced compared to wild-type

hearing/vestibular/ear
• in a model of induced pneumococcal meningitis-associated labyrinthitis, homozygotes exhibit significantly less hearing impairment at 24 hrs post-infection in response to click, 1- or 10-kHz stimuli relative to wild-type control mice

nervous system
• improved differentiation of progenitor cells into neurons
• survival of newly formed neurons is reduced
• after cold induced cortical injury, recruitment of neutrophiles to lesion site is reduced by 85% in comparison to controls
• cold induced cortical lesion volume is reduced by 25% compared to controls
• fewer cortical cells have damaged DNA compared to controls after cold induced cortical injury

digestive/alimentary system
• gross rectal bleeding 5 days after induction of colonic inflammation with dextran sodium sulfate
• increased number of apoptotic intestinal epithelial cells

renal/urinary system
• moderately protected from ischemia reperfusion injury as measured by serum creatinine levels 24 hours after injury

cardiovascular system
• gross rectal bleeding 5 days after induction of colonic inflammation with dextran sodium sulfate

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Coronavirus infectious disease DOID:0080599 J:162707


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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last database update
09/14/2021
MGI 6.17
The Jackson Laboratory