Phenotypes associated with this allele

• Allele Symbol: Myd88^tm1Aki
• Allele Name: targeted mutation 1, Shizuo Akira
• Allele ID: MGI:2385681
• Summary: 27 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Myd88^tm1Aki/Myd88^tm1Aki	B6.129-Myd88^tm1Aki	MGI:5447806
hm2	Myd88^tm1Aki/Myd88^tm1Aki	B6.129P2-Myd88^tm1Aki	MGI:3577712
hm3	Myd88^tm1Aki/Myd88^tm1Aki	C.129P2-Myd88^tm1Aki	MGI:5297118
hm4	Myd88^tm1Aki/Myd88^tm1Aki	involves: 129P2/OlaHsd	MGI:3694811
hm5	Myd88^tm1Aki/Myd88^tm1Aki	involves: 129P2/OlaHsd * C57BL/6	MGI:3707236
hm6	Myd88^tm1Aki/Myd88^tm1Aki	Not Specified	MGI:3039441
cn7	Fadd^tm1Mpa/Fadd^tm1Mpa Myd88^tm1Aki/Myd88^tm1Aki Tg(Vil1-cre)997Gum/0	B6.Cg-Fadd^tm1Mpa Myd88^tm1Aki Tg(Vil1-cre)997Gum	MGI:5293405
cn8	Myd88^tm1Aki/Myd88^tm1Aki Otulin^tm1c(EUCOMM)Hmgu/Otulin^tm1c(EUCOMM)Hmgu Tg(KRT14-cre)1Cgn/0	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6N * DBA/2	MGI:7256624
cn9	Myd88^tm1Aki/Myd88^tm1Aki Tnfaip3^tm1.1Gvl/Tnfaip3^tm1.1Gvl Tg(Vil1-cre)997Gum/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:4829678
cx10	Ifnar1^tm1Agt/Ifnar1^tm1Agt Myd88^tm1Aki/Myd88^+	B6.129-Myd88^tm1Aki Ifnar1^tm1Agt	MGI:5432885
cx11	Ifnar1^tm1Agt/Ifnar1^tm1Agt Myd88^tm1Aki/Myd88^tm1Aki	B6.129-Myd88^tm1Aki Ifnar1^tm1Agt	MGI:5432884
cx12	Myd88^tm1Aki/Myd88^tm1Aki Ticam1^tm1Aki/Ticam1^+	B6.129P2-Myd88^tm1Aki Ticam1^tm1Aki	MGI:5432883
cx13	Myd88^tm1Aki/Myd88^tm1Aki Ticam1^tm1Aki/Ticam1^tm1Aki	B6.129P2-Myd88^tm1Aki Ticam1^tm1Aki	MGI:5432882
cx14	Igh-J^tm1(Ighel)Cys/Igh-J^tm1(Ighel)Cys Myd88^tm1Aki/Myd88^tm1Aki Igkj1^tm1(IgkHyHEL10)Mnz/0	involves: 129P2/OlaHsd	MGI:3694812
cx15	Ifna6^tm1Aki/Ifna6^+ Myd88^tm1Aki/Myd88^tm1Aki	involves: 129P2/OlaHsd	MGI:3808910
cx16	Myd88^tm1Aki/Myd88^tm1Aki Tg(Vil-Myd88)#Lvh/0	involves: 129P2/OlaHsd	MGI:5297576
cx17	Myd88^tm1Aki/Myd88^tm1Aki Ticam1^tm1Aki/Ticam1^tm1Aki	involves: 129P2/OlaHsd	MGI:5317150
cx18	Ifnar1^tm1Agt/Ifnar1^tm1Agt Myd88^tm1Aki/Myd88^tm1Aki	involves: 129P2/OlaHsd * 129S2/SvPas	MGI:4950286
cx19	Clec7a^tm1Yiw/Clec7a^tm1Yiw Myd88^tm1Aki/Myd88^tm1Aki	involves: 129P2/OlaHsd * BALB/cA * C57BL/6J	MGI:3696862
cx20	Myd88^tm1Aki/Myd88^tm1Aki Tradd^tm1.1Mpa/Tradd^tm1.1Mpa	involves: 129P2/OlaHsd * BALB/cJ * C57BL/6	MGI:3807673
cx21	Arih2^tm1Mak/Arih2^tm1Mak Myd88^tm1Aki/Myd88^tm1Aki	involves: 129P2/OlaHsd * C57BL/6	MGI:5463667
cx22	Myd88^tm1Aki/Myd88^tm1Aki Unc93b1^tm1.1Kmiy/Unc93b1^tm1.1Kmiy	involves: 129P2/OlaHsd * C57BL/6	MGI:5140972
cx23	Myd88^tm1Aki/Myd88^tm1Aki Sh3bp2^tm1.1Ics/Sh3bp2^tm1.1Ics	involves: 129P2/OlaHsd * C57BL/6	MGI:5701642
cx24	Myd88^tm1Aki/Myd88^tm1Aki Tg(IghelMD4)4Ccg/0 Tg(KLK4mHEL)6Ccg/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3694808
cx25	Ticam1^Lps2/Ticam1^Lps2 Myd88^tm1Aki/Myd88^tm1Aki	involves: 129P2/OlaHsd * C57BL/6	MGI:2680623
cx26	Myd88^tm1Aki/Myd88^tm1Aki Tnip1^tm1.1Pcoh/Tnip1^tm1.1Pcoh	involves: 129P2/OlaHsd * C57BL/6	MGI:5296232
cx27	Myd88^tm1Aki/Myd88^tm1Aki Tank^tm1Aki/Tank^tm1Aki	involves: 129/Sv * 129P2/OlaHsd * C57BL/6	MGI:4355833

Genotype
MGI:5447806

hm1

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki
• Genetic Background: B6.129-Myd88^tm1Aki

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

immune system

decreased interleukin-6 secretion ( J:189854 )

• in bone marrow-derived macrophage exposed to sialylated C. jejuni

decreased tumor necrosis factor secretion ( J:189854 )

• in bone marrow-derived macrophage exposed to sialylated C. jejuni

abnormal susceptibility to bacterial infection ( J:189854 )

• bone marrow-derived macrophage exposed to sialylated C. jejuni exhibit reduced phagocytosis and production of TNF-alpha and IL6 compared with wild-type cells

• however, phagocytosis of sialylated bacteria is normal

Genotype
MGI:3577712

hm2

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki
• Genetic Background: B6.129P2-Myd88^tm1Aki

respiratory system

bronchiolitis ( J:162707 )

• rMA15 SARS-CoV-infected mice show denuding bronchiolitis not seen in wild-type mice

mortality/aging

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:162707 )

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

cellular

increased apoptosis ( J:102879 )

• 5 days after lung injury, mutants show significantly increased numbers of apoptotic lung epithelial and inflammatory cells

abnormal dendritic cell differentiation ( J:139001 )

• dendritic cell maturation fails to occur in vivo upon exposure to TLR9 agonists

abnormal neuron differentiation ( J:129957 )

• improved differentiation of progenitor cells into neurons

• survival of newly formed neurons is reduced

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:102879 )

• knockout mice are more susceptible to bleomycin-induced lung injury

decreased susceptibility to kidney reperfusion injury ( J:146120 )

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

immune system

abnormal dendritic cell differentiation ( J:139001 )

• dendritic cell maturation fails to occur in vivo upon exposure to TLR9 agonists

increased dendritic cell number ( J:116763 )

• increased numbers of dendritic cells in brains of mice infected with Plasmodium

abnormal immune system physiology ( J:121070 )

• response to LPS and CpG is completely abrogated

abnormal T cell physiology ( J:97662 )

• 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

abnormal dendritic cell physiology ( J:116670 , J:118954 )

• 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)

abnormal cytokine secretion ( J:116670 , J:162707 )

• 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)

abnormal chemokine secretion ( J:102879 )

• hyaluronan fragment-induced expression of chemokines by peritoneal macrophages is completely abolished in double knockout mice

decreased interferon-alpha secretion ( J:97662 )

• CpG-A or RNA polyuridylic acid induced production of interferon-alpha was abolished in plasmacytoid dendritic cells

decreased interferon-gamma secretion ( J:116763 , J:118954 )

• 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)

decreased interleukin-12 secretion ( J:116670 )

• after stimulation with zymosan, TNF production is significantly reduced in Myd88-deficient animals

decreased interleukin-12b secretion ( J:116763 , J:118954 )

• 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)

decreased interleukin-6 secretion ( J:118954 , J:121070 )

• 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)

decreased tumor necrosis factor secretion ( J:116670 , J:116763 , 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)

decreased inflammatory response ( J:123946 )

• 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

bronchiolitis ( J:162707 )

• rMA15 SARS-CoV-infected mice show denuding bronchiolitis not seen in wild-type mice

abnormal innate immunity ( J:162707 )

• 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

abnormal NK cell physiology ( J:139001 )

• NK cells fail to make IFN-gamma in response to injections of TLR9 agonists

abnormal macrophage physiology ( J:116670 )

• 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

abnormal response to infection ( J:121070 )

• 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

decreased susceptibility to parasitic infection ( J:116763 )

• resistant to cerebral malaria but eventually die of extremely high parasitemia

increased susceptibility to Coronaviridae infection ( J:162707 )

• 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

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:162707 )

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

increased susceptibility to Picornaviridae infection ( J:97662 )

• increased susceptibility to encephalomyocarditis virus (EMCV) infection compared to wildtype

hematopoietic system

abnormal dendritic cell differentiation ( J:139001 )

• dendritic cell maturation fails to occur in vivo upon exposure to TLR9 agonists

increased dendritic cell number ( J:116763 )

• increased numbers of dendritic cells in brains of mice infected with Plasmodium

abnormal NK cell physiology ( J:139001 )

• NK cells fail to make IFN-gamma in response to injections of TLR9 agonists

abnormal T cell physiology ( J:97662 )

• 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

abnormal macrophage physiology ( J:116670 )

• 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

abnormal susceptibility to hearing loss ( J:123946 )

• 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

abnormal neuron differentiation ( J:129957 )

• improved differentiation of progenitor cells into neurons

• survival of newly formed neurons is reduced

abnormal nervous system physiology ( J:122826 )

• 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

rectal hemorrhage ( J:128329 )

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

abnormal enterocyte morphology ( J:128329 )

• increased number of apoptotic intestinal epithelial cells

renal/urinary system

decreased susceptibility to kidney reperfusion injury ( J:146120 )

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

cardiovascular system

rectal hemorrhage ( J:128329 )

• 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

Genotype
MGI:5297118

hm3

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki
• Genetic Background: C.129P2-Myd88^tm1Aki

immune system

decreased susceptibility to induced arthritis ( J:178054 )

• in response to peptidoglycan or muramyl dipeptide (MDP), mice fail to develop arthritis unlike similarly treated wild-type mice

skeleton

decreased susceptibility to induced arthritis ( J:178054 )

• in response to peptidoglycan or muramyl dipeptide (MDP), mice fail to develop arthritis unlike similarly treated wild-type mice

Genotype
MGI:3694811

hm4

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki
• Genetic Background: involves: 129P2/OlaHsd

liver/biliary system

decreased liver tumor incidence ( J:103464 )

• resistant to Propionibacterium acnes induced liver granulomas

immune system

increased susceptibility to induced colitis ( J:167340 )

• highly susceptible to dextran sodium sulfate induced colitis

abnormal neutrophil physiology ( J:145345 )

• LPS-stimulated reactive oxygen intermediate (ROI) production by neutrophils is blocked compared to in similarly treated wild-type cells

• however, ROI production in response to PMA stimulation is normal

increased IgA level ( J:210086 )

• antibiotic treated mice infected with non-invasive Salmonella exhibit increased levels of Salmonella-specific IgA, but not IgG as compared to littermate controls

increased IgE level ( J:115059 )

• serum levels are elevated compared to wild-type

increased IgG1 level ( J:115059 )

• serum levels of IgG1 are elevated compared to wild-type

abnormal macrophage physiology ( J:174941 )

• absence of rEA stimulated activation of macrophages unlike in wild-type controls

abnormal cytokine level ( J:174941 )

• absence of rEA stimulated increase in cytokine and chemokine levels

abnormal interferon level ( J:137522 )

• decreased serum interferon alpha level following infection with Japanese encephalitis virus but not as severe as in mice homozygous for Ddx58^tm1Aki

abnormal tumor necrosis factor level ( J:103464 , J:124334 )

• Propionibacterium acnes and Tlr2 ligands fail to induce TNF alpha (J:103464)

• reduced TNF alpha production in response to both primary and secondary necrotic cells (J:124334)

decreased circulating tumor necrosis factor level ( J:139030 )

• in response to LPS stimulation; however, detectable levels of TNF are present

• impairment is not as severe as in mice homozygous for both Myd88^tm1Aki and Tradd^tm1.1Mpa

abnormal dendritic cell physiology ( J:137522 , J:174941 )

• profound defect in interferon alpha production in response to encephalomyocarditis virus in B220+ pDCs (J:137522)

• absence of Eimeria tenella derived antigen (rEA) stimulated activation of dendritic cells unlike in wild-type controls (J:174941)

• dendritic cells fail to produce higher levels of cytokines when stimulated with LPS, R848 or ODN2006 unlike wild-type cells (J:174941)

abnormal cytokine secretion ( J:167340 )

• flagellin stimulated primary intestinal epithelial cells display inhibited production of keratinocyte-derived cytokine and macrophage inflammatory protein 3 alpha

• IL-1beta fails to stimulate keratinocyte-derived cytokine production

decreased interferon-alpha secretion ( J:144400 )

• bone marrow-derived plasmacytoid dendritic cells infected with a low dose of murine hepatitis virus A59 are not able to produce IFN-alpha compared to wild-type mice that show IFN-alpha production

decreased interferon-gamma secretion ( J:210086 )

• antibiotic treated mice infected with non-invasive Salmonella exhibit decreased levels of interferon gamma in the mesenteric lymph nodes as compared to littermate controls

decreased interleukin-6 secretion ( J:167340 )

• flagellin stimulated primary intestinal epithelial cells display inhibited production

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:105435 )

• resistant to myelin oligodendrocyte glycoprotein injection

• no apparent inflammation in the spinal cord

increased susceptibility to bacterial infection ( J:210086 )

• antibiotic treated mice infected with non-invasive Salmonella exhibit increased bacterial counts in the mesenteric lymph nodes as compared to littermate controls

increased susceptibility to Picornaviridae infection ( J:137522 )

• modestly increased susceptibility of encephalomyocarditis virus induced lethality

• but susceptibility to Japanese encephalitis virus is similar to controls

hematopoietic system

hematopoietic system phenotype ( J:135830 )

N • B cell apoptosis in Peyer's patch is not observed after bile duct ligation

abnormal neutrophil physiology ( J:145345 )

• LPS-stimulated reactive oxygen intermediate (ROI) production by neutrophils is blocked compared to in similarly treated wild-type cells

• however, ROI production in response to PMA stimulation is normal

increased IgA level ( J:210086 )

• antibiotic treated mice infected with non-invasive Salmonella exhibit increased levels of Salmonella-specific IgA, but not IgG as compared to littermate controls

increased IgE level ( J:115059 )

• serum levels are elevated compared to wild-type

increased IgG1 level ( J:115059 )

• serum levels of IgG1 are elevated compared to wild-type

abnormal macrophage physiology ( J:174941 )

• absence of rEA stimulated activation of macrophages unlike in wild-type controls

homeostasis/metabolism

abnormal glucose homeostasis ( J:124334 )

• resistant to STZ induced diabetes

hyperglycemia ( J:148283 )

• more prone to hyperglycemia after low doses of streptozotocin

abnormal cytokine level ( J:174941 )

• absence of rEA stimulated increase in cytokine and chemokine levels

abnormal interferon level ( J:137522 )

• decreased serum interferon alpha level following infection with Japanese encephalitis virus but not as severe as in mice homozygous for Ddx58^tm1Aki

abnormal tumor necrosis factor level ( J:103464 , J:124334 )

• Propionibacterium acnes and Tlr2 ligands fail to induce TNF alpha (J:103464)

• reduced TNF alpha production in response to both primary and secondary necrotic cells (J:124334)

decreased circulating tumor necrosis factor level ( J:139030 )

• in response to LPS stimulation; however, detectable levels of TNF are present

• impairment is not as severe as in mice homozygous for both Myd88^tm1Aki and Tradd^tm1.1Mpa

neoplasm

decreased liver tumor incidence ( J:103464 )

• resistant to Propionibacterium acnes induced liver granulomas

respiratory system

abnormal respiratory system physiology ( J:147534 )

• bronchoalveolar protein levels are increased by ozone exposure

• ozone induced increase in bronchoalveolar cell counts are less than in controls at 3 hours but not 24 hours

abnormal airway responsiveness ( J:147534 )

• ozone exposure does not lead to hyperresponsiveness

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:148283 )

• beta cell volume as a percentage of pancreas volume is significantly reduced

• insulin content reduced

decreased pancreatic beta cell mass ( J:148283 )

small pancreatic islets ( J:148283 )

• islet size is reduced

• number of islet is normal

abnormal pancreatic beta cell physiology ( J:148283 )

• increased beta cell apoptosis

vision/eye

abnormal retina progenitor cell morphology ( J:141070 )

• more proliferating cells in the retina at 6 days of age

• neuronal differentiation of precursors hearing/vestibular/ear

digestive/alimentary system

digestive/alimentary phenotype ( J:177506 )

N • mice exhibit normal mucus production

abnormal gut flora balance ( J:177506 )

• mice exhibit a 100-fold higher mucosal bacterial loads compared with wild-type mice

• however, luminal bacterial loads are normal

abnormal enterocyte physiology ( J:167340 )

• flagellin stimulated primary intestinal epithelial cells display inhibited production of keratinocyte-derived cytokine, macrophage inflammatory protein 3 alpha, and IL-6

increased susceptibility to induced colitis ( J:167340 )

• highly susceptible to dextran sodium sulfate induced colitis

Genotype
MGI:3707236

hm5

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

immune system

immune system phenotype ( J:132662 )

N • the immunogenicity generated by a DNA vaccine is normal in these mice

decreased IgG level ( J:137066 )

• IgG2c production is considerably impaired at 7 and 11 weeks

decreased IgG2b level ( J:137066 )

• reduced in serum at 7 and 11 weeks of age

decreased IgG3 level ( J:137066 )

• significantly reduced in serum at 7 and 11 weeks of age

abnormal macrophage physiology ( J:117688 , J:141143 )

• macrophages do not produce TNFalpha or Il10 in response to a Tlr2 agonist, and a reduced response to heat-killed S. aureus (J:117688)

• bone marrow-derived macrophages fail to respond to Clec4e (Mincle) stimulation (J:141143)

abnormal dendritic cell physiology ( J:122394 )

abnormal cytokine secretion ( J:117688 )

• after stimulation with zymosan, bone marrow-derived dendritic cells produce much less TNF and Il-6, while Il-12 production is slightly lower

• stimulation with NaClO-oxidized zymosan does not affect cytokine response

abnormal chemokine secretion ( J:141143 )

• bone marrow-derived macrophages fail to secrete MIP-2 to Clec4e (Mincle) stimulation

decreased interleukin-1 beta secretion ( J:124226 )

• following stimulation with LPS, peritoneal macrophages fail to produce IL-1-beta

decreased interleukin-6 secretion ( J:147023 )

• production is suppressed in response to E coli

• Il10 production is unaffected

homeostasis/metabolism

decreased incidence of tumors by chemical induction ( J:162097 )

• skin cancers induced using croton oil and 7,12-dimethylbenz(a)anthracene

• reduced number of papillomas and carcinomas relative to controls

neoplasm

decreased incidence of tumors by chemical induction ( J:162097 )

• skin cancers induced using croton oil and 7,12-dimethylbenz(a)anthracene

• reduced number of papillomas and carcinomas relative to controls

hematopoietic system

decreased IgG level ( J:137066 )

• IgG2c production is considerably impaired at 7 and 11 weeks

decreased IgG2b level ( J:137066 )

• reduced in serum at 7 and 11 weeks of age

decreased IgG3 level ( J:137066 )

• significantly reduced in serum at 7 and 11 weeks of age

abnormal macrophage physiology ( J:117688 , J:141143 )

• macrophages do not produce TNFalpha or Il10 in response to a Tlr2 agonist, and a reduced response to heat-killed S. aureus (J:117688)

• bone marrow-derived macrophages fail to respond to Clec4e (Mincle) stimulation (J:141143)

Genotype
MGI:3039441

hm6

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki
• Genetic Background: Not Specified

cellular

decreased B cell proliferation ( J:96773 )

• splenocytes showed a defect in proliferation in response to the TLR4 ligand lipopolysaccharide (LPS), bacterial lipopeptide (BLP) that signals through the TLR1-TLR2 heterodimer, the TLR9 ligand unmethylated CpG DNA (CpG) and to the TLR7 ligand resiquimod (R-848)

immune system

decreased B cell proliferation ( J:96773 )

• splenocytes showed a defect in proliferation in response to the TLR4 ligand lipopolysaccharide (LPS), bacterial lipopeptide (BLP) that signals through the TLR1-TLR2 heterodimer, the TLR9 ligand unmethylated CpG DNA (CpG) and to the TLR7 ligand resiquimod (R-848)

abnormal NK cell physiology ( J:88906 )

• NK and NK-T cell activation is significantly lower compared to C57BL/6 wild-type controls during mouse cytomegalovirus infection

abnormal T cell physiology ( J:96773 )

• thymocytes failed to proliferate in response to IL-1

abnormal NK T cell physiology ( J:88906 )

• NK and NK-T cell activation is significantly lower compared to C57BL/6 wild-type controls during mouse cytomegalovirus infection

abnormal macrophage physiology ( J:96773 )

• activation of NF-kappaB, JNK, p38 and ERK in bone marrow derived macrophages was delayed in response to LPS and absent in response to BLP and CpG

abnormal dendritic cell physiology ( J:96773 )

• dendritic cells produced barely detectable amounts of cytokines in response to LPS or CpG

• dendritic cells mature only in response to LPS but not CpG

abnormal cytokine secretion ( J:88906 , J:89257 )

• type 1 IFN, IFNgamma and IL-12 p40 levels are decreased compared to C57BL/6 wild-type controls following sublethal viral infection (J:88906)

• IFNalpha was not secreted after infection with vesicular stomatitis virus (a ssRNA virus) (J:89257)

increased susceptibility to Herpesvirales infection ( J:88906 )

• viral loads and mortality are significantly higher after mouse cytomegalovirus infection compared to C57BL/6 wild-type controls

hematopoietic system

decreased B cell proliferation ( J:96773 )

• splenocytes showed a defect in proliferation in response to the TLR4 ligand lipopolysaccharide (LPS), bacterial lipopeptide (BLP) that signals through the TLR1-TLR2 heterodimer, the TLR9 ligand unmethylated CpG DNA (CpG) and to the TLR7 ligand resiquimod (R-848)

abnormal NK cell physiology ( J:88906 )

• NK and NK-T cell activation is significantly lower compared to C57BL/6 wild-type controls during mouse cytomegalovirus infection

abnormal T cell physiology ( J:96773 )

• thymocytes failed to proliferate in response to IL-1

abnormal NK T cell physiology ( J:88906 )

• NK and NK-T cell activation is significantly lower compared to C57BL/6 wild-type controls during mouse cytomegalovirus infection

abnormal macrophage physiology ( J:96773 )

• activation of NF-kappaB, JNK, p38 and ERK in bone marrow derived macrophages was delayed in response to LPS and absent in response to BLP and CpG

Genotype
MGI:5293405

cn7

• Allelic Composition: Fadd^tm1Mpa/Fadd^tm1Mpa; Myd88^tm1Aki/Myd88^tm1Aki; Tg(Vil1-cre)997Gum/0
• Genetic Background: B6.Cg-Fadd^tm1Mpa Myd88^tm1Aki Tg(Vil1-cre)997Gum

digestive/alimentary system

digestive/alimentary phenotype ( J:175865 )

N • mice do not develop colitis

decreased Paneth cell number ( J:175865 )

• reduced numbers

cecum inflammation ( J:175865 )

endocrine/exocrine glands

decreased Paneth cell number ( J:175865 )

• reduced numbers

immune system

cecum inflammation ( J:175865 )

Genotype
MGI:7256624

cn8

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki; Otulin^{tm1c(EUCOMM)Hmgu}/Otulin^{tm1c(EUCOMM)Hmgu}; Tg(KRT14-cre)1Cgn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6N * DBA/2

integument

integument phenotype ( J:312394 )

N • no skin lesions and normal epidermal thickness

Genotype
MGI:4829678

cn9

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki; Tnfaip3^tm1.1Gvl/Tnfaip3^tm1.1Gvl; Tg(Vil1-cre)997Gum/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

digestive/alimentary system

increased enterocyte apoptosis ( J:163410 )

• in DDS-treated mice

increased susceptibility to induced colitis ( J:163410 )

• mice exhibit increased susceptibility compared to in Myd88^tm1Aki/Myd88⁺ Tnfaip3^tm1.1Gvl Tg(Vil-cre)997Gum mice or Myd88^tm1Aki homozygotes

immune system

increased susceptibility to induced colitis ( J:163410 )

• mice exhibit increased susceptibility compared to in Myd88^tm1Aki/Myd88⁺ Tnfaip3^tm1.1Gvl Tg(Vil-cre)997Gum mice or Myd88^tm1Aki homozygotes

cellular

increased enterocyte apoptosis ( J:163410 )

• in DDS-treated mice

Genotype
MGI:5432885

cx10

• Allelic Composition: Ifnar1^tm1Agt/Ifnar1^tm1Agt; Myd88^tm1Aki/Myd88⁺
• Genetic Background: B6.129-Myd88^tm1Aki Ifnar1^tm1Agt

immune system

increased susceptibility to parasitic infection ( J:140485 )

• in cultured bone marrow dendritic cells from mice infected with Trypanosoma cruzi the number of trypomastigotes released into the supernatant is slightly increased and the replication within macrophages is slightly enhanced compared to controls

• slight increase in the number of trypomastigotes in the serum of T. cruzi infected mice

Genotype
MGI:5432884

cx11

• Allelic Composition: Ifnar1^tm1Agt/Ifnar1^tm1Agt; Myd88^tm1Aki/Myd88^tm1Aki
• Genetic Background: B6.129-Myd88^tm1Aki Ifnar1^tm1Agt

mortality/aging

increased susceptibility to parasitic infection induced morbidity/mortality ( J:140485 )

• all mice die within 19 days of infection with T. cruzi

immune system

increased susceptibility to parasitic infection ( J:140485 )

• in cultured bone marrow dendritic cells from mice infected with Trypanosoma cruzi the number of trypomastigotes released into the supernatant is considerably increased and the replication within macrophages is markedly enhanced compared to controls

• serum parasite counts continue to increase after day 13 and reach a much higher level by 15 days post infection

increased susceptibility to parasitic infection induced morbidity/mortality ( J:140485 )

• all mice die within 19 days of infection with T. cruzi

Genotype
MGI:5432883

cx12

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki; Ticam1^tm1Aki/Ticam1⁺
• Genetic Background: B6.129P2-Myd88^tm1Aki Ticam1^tm1Aki

mortality/aging

increased susceptibility to parasitic infection induced morbidity/mortality ( J:140485 )

• start to die around 15 days and about half die within 19 days post T. cruzi infection unlike controls that survive for more than 19 days

immune system

decreased macrophage cytokine production ( J:140485 )

• severely reduced production of TNF in Trypanosoma cruzi infected macrophages

decreased macrophage nitric oxide production ( J:140485 )

• severely reduced in Trypanosoma cruzi infected macrophages

increased susceptibility to parasitic infection ( J:140485 )

• in cultured bone marrow dendritic cells from mice infected with Trypanosoma cruzi the number of trypomastigotes released into the supernatant is increased and the replication within macrophages is slightly enhanced compared to controls

increased susceptibility to parasitic infection induced morbidity/mortality ( J:140485 )

• start to die around 15 days and about half die within 19 days post T. cruzi infection unlike controls that survive for more than 19 days

homeostasis/metabolism

decreased macrophage nitric oxide production ( J:140485 )

• severely reduced in Trypanosoma cruzi infected macrophages

hematopoietic system

decreased macrophage cytokine production ( J:140485 )

• severely reduced production of TNF in Trypanosoma cruzi infected macrophages

decreased macrophage nitric oxide production ( J:140485 )

• severely reduced in Trypanosoma cruzi infected macrophages

Genotype
MGI:5432882

cx13

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki; Ticam1^tm1Aki/Ticam1^tm1Aki
• Genetic Background: B6.129P2-Myd88^tm1Aki Ticam1^tm1Aki

mortality/aging

increased susceptibility to parasitic infection induced morbidity/mortality ( J:140485 )

• all mice die within 19 days of infection with T. cruzi

immune system

decreased macrophage cytokine production ( J:140485 )

• severely reduced production of TNF in Trypanosoma cruzi infected macrophages

decreased macrophage nitric oxide production ( J:140485 )

• severely reduced in Trypanosoma cruzi infected macrophages

increased susceptibility to parasitic infection ( J:140485 )

• in cultured bone marrow dendritic cells from mice infected with Trypanosoma cruzi the number of trypomastigotes released into the supernatant is considerably increased and the replication within macrophages is markedly enhanced compared to controls

• serum parasite counts continue to increase after day 13 and reach a much higher level by 15 days post infection

increased susceptibility to parasitic infection induced morbidity/mortality ( J:140485 )

• all mice die within 19 days of infection with T. cruzi

homeostasis/metabolism

decreased macrophage nitric oxide production ( J:140485 )

• severely reduced in Trypanosoma cruzi infected macrophages

hematopoietic system

decreased macrophage cytokine production ( J:140485 )

• severely reduced production of TNF in Trypanosoma cruzi infected macrophages

decreased macrophage nitric oxide production ( J:140485 )

• severely reduced in Trypanosoma cruzi infected macrophages

Genotype
MGI:3694812

cx14

• Allelic Composition: Igh-J^{tm1(Ighel)Cys}/Igh-J^{tm1(Ighel)Cys}; Myd88^tm1Aki/Myd88^tm1Aki; Igkj1^{tm1(IgkHyHEL10)Mnz}/0
• Genetic Background: involves: 129P2/OlaHsd

immune system

increased IgM level ( J:115059 )

• serum levels are increased compared to wild-type

hematopoietic system

increased IgM level ( J:115059 )

• serum levels are increased compared to wild-type

Genotype
MGI:3808910

cx15

• Allelic Composition: Ifna6^tm1Aki/Ifna6⁺; Myd88^tm1Aki/Myd88^tm1Aki
• Genetic Background: involves: 129P2/OlaHsd

immune system

abnormal plasmacytoid dendritic cell morphology ( J:124340 )

• there is more than a 10-fold drop in the percentage of plasmacytoid dendritic cells that are GFP⁺ in response to Newcastle disease virus (NDV) infection when compared to controls

decreased interferon-alpha secretion ( J:124340 )

• levels of IFN-alpha are decreased 2 to 12 hours after infection with NDV compared to controls

hematopoietic system

abnormal plasmacytoid dendritic cell morphology ( J:124340 )

• there is more than a 10-fold drop in the percentage of plasmacytoid dendritic cells that are GFP⁺ in response to Newcastle disease virus (NDV) infection when compared to controls

Genotype
MGI:5297576

cx16

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki; Tg(Vil-Myd88)#Lvh/0
• Genetic Background: involves: 129P2/OlaHsd

digestive/alimentary system

digestive/alimentary phenotype ( J:177506 )

N • the separation between microbiota and host tissue is restored

Genotype
MGI:5317150

cx17

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki; Ticam1^tm1Aki/Ticam1^tm1Aki
• Genetic Background: involves: 129P2/OlaHsd

immune system

abnormal macrophage physiology ( J:174941 )

• absence of Eimeria tenella derived antigen (rEA) stimulated activation of macrophages unlike in wild-type controls

abnormal dendritic cell physiology ( J:174941 )

• absence of Eimeria tenella derived antigen (rEA) stimulated activation of dendritic cells unlike in wild-type controls

• dendritic cells fail to produce higher levels of cytokines when stimulated with LPS, R848 or ODN2006 unlike wild-type cells

hematopoietic system

abnormal macrophage physiology ( J:174941 )

• absence of Eimeria tenella derived antigen (rEA) stimulated activation of macrophages unlike in wild-type controls

Genotype
MGI:4950286

cx18

• Allelic Composition: Ifnar1^tm1Agt/Ifnar1^tm1Agt; Myd88^tm1Aki/Myd88^tm1Aki
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas

immune system

abnormal leukocyte migration ( J:171379 )

• LPS-induced monocyte emigration is decreased compared to in similarly treated wild-type mice

cellular

abnormal leukocyte migration ( J:171379 )

• LPS-induced monocyte emigration is decreased compared to in similarly treated wild-type mice

hematopoietic system

abnormal leukocyte migration ( J:171379 )

• LPS-induced monocyte emigration is decreased compared to in similarly treated wild-type mice

Genotype
MGI:3696862

cx19

• Allelic Composition: Clec7a^tm1Yiw/Clec7a^tm1Yiw; Myd88^tm1Aki/Myd88^tm1Aki
• Genetic Background: involves: 129P2/OlaHsd * BALB/cA * C57BL/6J

immune system

abnormal dendritic cell physiology ( J:116670 )

• cytokine production elicited by zymosan or LPS stimulation is impaired

abnormal cytokine secretion ( J:116670 )

• LPS-induced cytokine production by BMDCs is almost abolished compared to controls and Myd88-sufficient mutants

• after stimulation with zymosan, TNF and Il12 production are significantly reduced in BMDCs of Myd88-deficient animals

Genotype
MGI:3807673

cx20

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki; Tradd^tm1.1Mpa/Tradd^tm1.1Mpa
• Genetic Background: involves: 129P2/OlaHsd * BALB/cJ * C57BL/6

immune system

decreased circulating tumor necrosis factor level ( J:139030 )

• in response to LPS stimulation

• impairment is more severe than in either single homozygote

homeostasis/metabolism

decreased circulating tumor necrosis factor level ( J:139030 )

• in response to LPS stimulation

• impairment is more severe than in either single homozygote

Genotype
MGI:5463667

cx21

• Allelic Composition: Arih2^tm1Mak/Arih2^tm1Mak; Myd88^tm1Aki/Myd88^tm1Aki
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

abnormal survival ( J:191066 )

• survival is prolonged compared to mutant mice wild-type for Myd88

Genotype
MGI:5140972

cx22

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki; Unc93b1^tm1.1Kmiy/Unc93b1^tm1.1Kmiy
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

hematopoietic system

hematopoietic system phenotype ( J:174308 )

N • platelet counts are normal

Genotype
MGI:5701642

cx23

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki; Sh3bp2^tm1.1Ics/Sh3bp2^tm1.1Ics
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

immune system

immune system phenotype ( J:221901 )

N • serum TNF-alpha levels are similar to wild-type levels

Genotype
MGI:3694808

cx24

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki; Tg(IghelMD4)4Ccg/0; Tg(KLK4mHEL)6Ccg/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

hematopoietic system

decreased mature B cell number ( J:115059 )

• a reduction in number of recirculating mature autoreactive B cells is observed compared to wild-type

increased B-1 B cell number ( J:115059 )

• more B1 cells are detected among peritoneal lymphocytes in double transgenic mutants compared to Tg(IghelMD4)4Ccg single transgenic mutants

immune system

decreased mature B cell number ( J:115059 )

• a reduction in number of recirculating mature autoreactive B cells is observed compared to wild-type

increased B-1 B cell number ( J:115059 )

• more B1 cells are detected among peritoneal lymphocytes in double transgenic mutants compared to Tg(IghelMD4)4Ccg single transgenic mutants

Genotype
MGI:2680623

cx25

• Allelic Composition: Ticam1^Lps2/Ticam1^Lps2; Myd88^tm1Aki/Myd88^tm1Aki
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

immune system

abnormal macrophage physiology ( J:84896 )

• no response to LPS in vitro

decreased tumor necrosis factor secretion ( J:84896 )

• TNF production by macrophages in response to LPS is abolished

hematopoietic system

abnormal macrophage physiology ( J:84896 )

• no response to LPS in vitro

Genotype
MGI:5296232

cx26

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki; Tnip1^tm1.1Pcoh/Tnip1^tm1.1Pcoh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

immune system

immune system phenotype ( J:176826 )

N • mice do not exhibit the autoimmune phenotype observed in Tnip1^tm1.1Pcoh homozygotes

Genotype
MGI:4355833

cx27

• Allelic Composition: Myd88^tm1Aki/Myd88^tm1Aki; Tank^tm1Aki/Tank^tm1Aki
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * C57BL/6

immune system

increased anti-double stranded DNA antibody level ( J:151757 )