Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N5F3pN1 Generation Definitions   Donating Investigator IMR Colony,   The Jackson Laboratory

Description
These mice possess loxP sites on either side of exon 3 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 3 deleted in the cre-expressing tissue(s).

When bred to a strain with inducible Cre recombinase expression in dendritic cells (see Stock No. 008068 for example), this mutant mouse strain may be useful in studies of Toll-like receptor signaling during immune responses.

When bred to a strain with Cre recombinase expression in hematopoietic cells (see Stock No. 008610 for example), this mutant mouse strain may be useful in studies of Toll-like receptor signaling and natural killer cells.

When bred to a strain with Cre recombinase expression in villi and crypt cells of the small and large intestines (see Stock No. 004586 for example), this mutant mouse strain may be useful in studies of microbial intestinal flora.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A FRT site flanked targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes (HSV-TK) and a diphtheria toxin A subunit cassette was utilized in the construction of this mutant. This selection cassette was inserted upstream of exon 3 of the targeted gene, and another loxP site was inserted downstream of exon 3. This construct was electroporated into 129P2/OlaHsd derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to transgenic mice (on a congenic C57BL/6 genetic background) expressing FLPe recombinase under the control of the actin beta (ACTB) promoter to remove the selection cassette. Mice that retained the loxP site flanked exon 3 (and residual single FRT site) were then backcrossed to C57BL/6J for 11 generations before arriving at The Jackson Laboratory (as Stock No. 008888). Upon arrival, some mice were backcrossed to BALB/cByJ inbred mice (Stock No. 001026) for at least 5 generations to generate this congenic strain (Stock No. 009108).

Control Information

	Control
	001026 BALB/cByJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Myd88^tm1Defr allele

008888	B6.129P2(SJL)-Myd88tm1Defr/J
012622	NOD.Cg-Myd88tm1Defr/J

View Strains carrying   Myd88^tm1Defr     (2 strains)

Strains carrying other alleles of Myd88

009088	B6.129P2(SJL)-Myd88tm1.1Defr/J
016133	C57BL/6-Tg(Defa2-Myd88)1Lvh/J
017481	C57BL/6-Tg(Vil1-Myd88)1Lvh/J

View Strains carrying other alleles of Myd88     (3 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Macroglobulinemia, Waldenstrom, Susceptibility to, 1; WM1   (MYD88) Myd88 Deficiency; MYD88D   (MYD88)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Myd88^tm1Defr/Myd88^tm1Defr Tg(Itgax-cre)1-1Reiz/0

        B6.Cg-Myd88^tm1Defr Tg(Itgax-cre)1-1Reiz   (conditional)

• immune system phenotype
• abnormal NK cell physiology
  • NK cells in vivo make much several fold less IFN-gamma in response to injections of TLR9 agonists   (MGI Ref ID J:139001)
  • there is also a reduction in IFN-gamma production upon LPS administration   (MGI Ref ID J:139001)
• abnormal T-helper 1 cell differentiation
  • less Th1 T cells develop when naïve antigen-specific T cells are transferred into these mice with cognate antigen and a TLR9 agonist   (MGI Ref ID J:139001)
• abnormal dendritic cell differentiation
  • dendritic cell maturation mediated by injections of TLR9 agonists is diminished in these mice   (MGI Ref ID J:139001)
  • maturation markers on DCs such as I-A^b, CD80, and CD86 have several fold lower expression than in controls   (MGI Ref ID J:139001)
• abnormal dendritic cell physiology
  • DCs fail to secrete cytokines in response to TLR9 agonists   (MGI Ref ID J:139001)
• • abnormal dendritic cell antigen presentation
    • naïve antigen-specific T cells expand at a much slower rate when transferred into these mice with cognate antigen and TLR9 agonist   (MGI Ref ID J:139001)
• decreased IgG1 level
  • antigen specific IgG1 levels are lower by almost an order of magnitude compared to controls after immunization with OVA-peptide and TLR9 agonist   (MGI Ref ID J:139001)
• decreased IgG2b level
  • antigen specific IgG2b levels are lower by an order of magnitude compared to controls after immunization with OVA-peptide and TLR9 agonist   (MGI Ref ID J:139001)
• decreased IgG2c level
  • antigen specific IgG2c levels are lower by several orders of magnitude than controls after immunization with OVA-peptide and TLR9 agonist   (MGI Ref ID J:139001)
• decreased circulating interleukin-12b level
  • mice fail to make IL-12p40 in response to the TLR9 agonist CpG-containing oligodeoxynucleotide ODN1826   (MGI Ref ID J:139001)
  • IL-12p40 production is reduced 5- to 30- fold in response to agonists to TLR1 +TLR2, TLR4, TLR5, TLR7, or TLR9   (MGI Ref ID J:139001)
• decreased circulating interleukin-6 level
  • circulating levels of IL-6 one hour after TLR9 stimulation is half that in wild-type controls   (MGI Ref ID J:139001)
• homeostasis/metabolism phenotype
• decreased circulating interleukin-12b level
  • mice fail to make IL-12p40 in response to the TLR9 agonist CpG-containing oligodeoxynucleotide ODN1826   (MGI Ref ID J:139001)
  • IL-12p40 production is reduced 5- to 30- fold in response to agonists to TLR1 +TLR2, TLR4, TLR5, TLR7, or TLR9   (MGI Ref ID J:139001)
• decreased circulating interleukin-6 level
  • circulating levels of IL-6 one hour after TLR9 stimulation is half that in wild-type controls   (MGI Ref ID J:139001)
• hematopoietic system phenotype
• abnormal T-helper 1 cell differentiation
  • less Th1 T cells develop when naïve antigen-specific T cells are transferred into these mice with cognate antigen and a TLR9 agonist   (MGI Ref ID J:139001)
• abnormal dendritic cell differentiation
  • dendritic cell maturation mediated by injections of TLR9 agonists is diminished in these mice   (MGI Ref ID J:139001)
  • maturation markers on DCs such as I-A^b, CD80, and CD86 have several fold lower expression than in controls   (MGI Ref ID J:139001)
• cellular phenotype
• abnormal T-helper 1 cell differentiation
  • less Th1 T cells develop when naïve antigen-specific T cells are transferred into these mice with cognate antigen and a TLR9 agonist   (MGI Ref ID J:139001)
• abnormal dendritic cell differentiation
  • dendritic cell maturation mediated by injections of TLR9 agonists is diminished in these mice   (MGI Ref ID J:139001)
  • maturation markers on DCs such as I-A^b, CD80, and CD86 have several fold lower expression than in controls   (MGI Ref ID J:139001)

Myd88^tm1Defr/Myd88^tm1Defr Tg(Vav1-cre)A2Kio/0

        involves: 129P2/OlaHsd * C57BL/6 * SJL   (conditional)

• immune system phenotype
• abnormal NK cell physiology
  • NK cells fail to make IFN-gamma in response to injections of TLR9 agonists   (MGI Ref ID J:139001)
  • NK cells in vivo have a blunted IFN-gamma response to LPS injections   (MGI Ref ID J:139001)

Myd88^tm1Defr/Myd88^tm1Defr Tg(Vil-cre)997Gum/0

        involves: 129P2/OlaHsd * C57BL/6J * SJL   (conditional)

• digestive/alimentary phenotype
• abnormal gut flora balance
  • mice exhibit a higher mucosal bacterial loads compared with Myd88^tm1Defr control mice but not as much as in Myd88 null or conditionally knocked-out mice   (MGI Ref ID J:177506)
  • however, luminal bacterial loads are normal   (MGI Ref ID J:177506)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cancer Research
Cre-lox System
      loxP-flanked Sequences
Growth Factors/Receptors/Cytokines

Cell Biology Research
Signal Transduction

Immunology, Inflammation and Autoimmunity Research
Growth Factors/Receptors/Cytokines
Intracellular Signaling Molecules

Research Tools
Cancer Research
      Cre-lox System
Cre-lox System
      loxP-flanked Sequences
Genetics Research
      Mutagenesis and Transgenesis
      Mutagenesis and Transgenesis: Cre-lox System
Immunology and Inflammation Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Myd88tm1Defr
Allele Name		targeted mutation 1, Anthony L DeFranco
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Myd88fl;
Mutation Made By		Anthony DeFranco,   UCSF
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Myd88, myeloid differentiation primary response gene 88
Chromosome		9
Gene Common Name(s)		MYD88D;
Molecular Note		Exon 3 was flanked by loxP sites by placing a FRT-flanked neo-cassette with a 3' loxP site upstream of exon 3 with an additional loxP site being placed downstream of exon 3. Founders were crossed with ACTB-FLPe mice to remove the neo selection cassette. Expression levels of Myd88 were unaffected by loxP insertion. Cre-recombination is predicted to excise exon 3 and create a null allele. [MGI Ref ID J:139001]

Genotyping

Genotyping Information

Genotyping Protocols

Myd88^tm1Defr, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Hou B; Reizis B; Defranco AL. 2008. Toll-like Receptors Activate Innate and Adaptive Immunity by using Dendritic Cell-Intrinsic and -Extrinsic Mechanisms. Immunity 29(2):272-82. [PubMed: 18656388]  [MGI Ref ID J:139001]

Additional References

Myd88^tm1Defr related

Abram CL; Roberge GL; Pao LI; Neel BG; Lowell CA. 2013. Distinct roles for neutrophils and dendritic cells in inflammation and autoimmunity in motheaten mice. Immunity 38(3):489-501. [PubMed: 23521885]  [MGI Ref ID J:195276]

Browne EP. 2011. Toll-like receptor 7 controls the anti-retroviral germinal center response. PLoS Pathog 7(10):e1002293. [PubMed: 21998589]  [MGI Ref ID J:183184]

Chang J; Burkett PR; Borges CM; Kuchroo VK; Turka LA; Chang CH. 2013. MyD88 is essential to sustain mTOR activation necessary to promote T helper 17 cell proliferation by linking IL-1 and IL-23 signaling. Proc Natl Acad Sci U S A 110(6):2270-5. [PubMed: 23341605]  [MGI Ref ID J:193828]

Du Y; Yang M; Lee S; Behrendt CL; Hooper LV; Saghatelian A; Wan Y. 2012. Maternal western diet causes inflammatory milk and TLR2/4-dependent neonatal toxicity. Genes Dev 26(12):1306-11. [PubMed: 22713870]  [MGI Ref ID J:184823]

Hammer GE; Turer EE; Taylor KE; Fang CJ; Advincula R; Oshima S; Barrera J; Huang EJ; Hou B; Malynn BA; Reizis B; DeFranco A; Criswell LA; Nakamura MC; Ma A. 2011. Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Nat Immunol 12(12):1184-93. [PubMed: 22019834]  [MGI Ref ID J:178962]

Henao-Mejia J; Elinav E; Jin C; Hao L; Mehal WZ; Strowig T; Thaiss CA; Kau AL; Eisenbarth SC; Jurczak MJ; Camporez JP; Shulman GI; Gordon JI; Hoffman HM; Flavell RA. 2012. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482(7384):179-85. [PubMed: 22297845]  [MGI Ref ID J:181354]

Hou B; Saudan P; Ott G; Wheeler ML; Ji M; Kuzmich L; Lee LM; Coffman RL; Bachmann MF; Defranco AL. 2011. Selective Utilization of Toll-like Receptor and MyD88 Signaling in B Cells for Enhancement of the Antiviral Germinal Center Response. Immunity 34(3):375-84. [PubMed: 21353603]  [MGI Ref ID J:170704]

Kirkland D; Benson A; Mirpuri J; Pifer R; Hou B; Defranco AL; Yarovinsky F. 2012. B Cell-Intrinsic MyD88 Signaling Prevents the Lethal Dissemination of Commensal Bacteria during Colonic Damage. Immunity 36(2):228-38. [PubMed: 22306056]  [MGI Ref ID J:181331]

Klose CS; Kiss EA; Schwierzeck V; Ebert K; Hoyler T; d'Hargues Y; Goppert N; Croxford AL; Waisman A; Tanriver Y; Diefenbach A. 2013. A T-bet gradient controls the fate and function of CCR6-RORgammat+ innate lymphoid cells. Nature 494(7436):261-5. [PubMed: 23334414]  [MGI Ref ID J:194555]

Le HT; Tran VG; Kim W; Kim J; Cho HR; Kwon B. 2012. IL-33 priming regulates multiple steps of the neutrophil-mediated anti-Candida albicans response by modulating TLR and dectin-1 signals. J Immunol 189(1):287-95. [PubMed: 22661085]  [MGI Ref ID J:188941]

Ochi A; Nguyen AH; Bedrosian AS; Mushlin HM; Zarbakhsh S; Barilla R; Zambirinis CP; Fallon NC; Rehman A; Pylayeva-Gupta Y; Badar S; Hajdu CH; Frey AB; Bar-Sagi D; Miller G. 2012. MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells. J Exp Med 209(9):1671-87. [PubMed: 22908323]  [MGI Ref ID J:191814]

Pihlgren M; Silva AB; Madani R; Giriens V; Waeckerle-Men Y; Fettelschoss A; Hickman DT; Lopez-Deber MP; Ndao DM; Vukicevic M; Buccarello AL; Gafner V; Chuard N; Reis P; Piorkowska K; Pfeifer A; Kundig TM; Muhs A; Johansen P. 2013. TLR4- and TRIF-dependent stimulation of B lymphocytes by peptide liposomes enables T cell-independent isotype switch in mice. Blood 121(1):85-94. [PubMed: 23144170]  [MGI Ref ID J:192819]

Raetz M; Hwang SH; Wilhelm CL; Kirkland D; Benson A; Sturge CR; Mirpuri J; Vaishnava S; Hou B; Defranco AL; Gilpin CJ; Hooper LV; Yarovinsky F. 2013. Parasite-induced T(H)1 cells and intestinal dysbiosis cooperate in IFN-gamma-dependent elimination of Paneth cells. Nat Immunol 14(2):136-42. [PubMed: 23263554]  [MGI Ref ID J:192614]

Rahman AH; Zhang R; Blosser CD; Hou B; Defranco AL; Maltzman JS; Wherry EJ; Turka LA. 2011. Antiviral memory CD8 T-cell differentiation, maintenance, and secondary expansion occur independently of MyD88. Blood 117(11):3123-30. [PubMed: 21233312]  [MGI Ref ID J:170518]

Rivas MN; Koh YT; Chen A; Nguyen A; Lee YH; Lawson G; Chatila TA. 2012. MyD88 is critically involved in immune tolerance breakdown at environmental interfaces of Foxp3-deficient mice. J Clin Invest 122(5):1933-47. [PubMed: 22466646]  [MGI Ref ID J:184544]

Subramanian M; Thorp E; Hansson GK; Tabas I. 2013. Treg-mediated suppression of atherosclerosis requires MYD88 signaling in DCs. J Clin Invest 123(1):179-88. [PubMed: 23257360]  [MGI Ref ID J:194509]

Tarallo V; Hirano Y; Gelfand BD; Dridi S; Kerur N; Kim Y; Cho WG; Kaneko H; Fowler BJ; Bogdanovich S; Albuquerque RJ; Hauswirth WW; Chiodo VA; Kugel JF; Goodrich JA; Ponicsan SL; Chaudhuri G; Murphy MP; Dunaief JL; Ambati BK; Ogura Y; Yoo JW; Lee DK; Provost P; Hinton DR; Nunez G; Baffi JZ; Kleinman ME; Ambati J. 2012. DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88. Cell 149(4):847-59. [PubMed: 22541070]  [MGI Ref ID J:186198]

Vaishnava S; Yamamoto M; Severson KM; Ruhn KA; Yu X; Koren O; Ley R; Wakeland EK; Hooper LV. 2011. The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine. Science 334(6053):255-8. [PubMed: 21998396]  [MGI Ref ID J:177506]

Zhang Y; Jones M; McCabe A; Winslow GM; Avram D; Macnamara KC. 2013. MyD88 Signaling in CD4 T Cells Promotes IFN-gamma Production and Hematopoietic Progenitor Cell Expansion in Response to Intracellular Bacterial Infection. J Immunol 190(9):4725-35. [PubMed: 23526822]  [MGI Ref ID J:195524]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	Mutant mice were bred to BALB/cByJ inbred mice (Stock No. 001026) for many generations to establish this congenic strain. When maintaining the live congenic colony, homozygous mice may be bred together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	001026 BALB/cByJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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