Strain Name:

C57BL/6-Tg(ML5sHEL)5Ccg/J

Stock Number:

002599

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Availability:

Cryopreserved - Ready for recovery

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 Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
GenerationF?+10N1p (16-JAN-05)
Generation Definitions
 
Donating Investigator Christopher Goodnow,   Stanford University School of Medicine

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the TgN(ML5sHEL)5Ccg transgene express a soluble form of hen egg lysozyme.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Tg(ML5sHEL)5Ccg allele
006610   NOD.B6-Tg(ML5sHEL)5Ccg/DvsJ
View Strains carrying   Tg(ML5sHEL)5Ccg     (1 strain)

View Strains carrying other alleles of Mt1     (15 strains)

Strains carrying other alleles of HEL
002598   C57BL/6-Tg(KLK4mHEL)6Ccg/J
004258   NOD.B6-Tg(KLK4mHEL)6Ccg/Dvs
006610   NOD.B6-Tg(ML5sHEL)5Ccg/DvsJ
View Strains carrying other alleles of HEL     (3 strains)

Strains carrying other alleles of Tg(ML5sHEL)5Ccg
006610   NOD.B6-Tg(ML5sHEL)5Ccg/DvsJ
View Strains carrying other alleles of Tg(ML5sHEL)5Ccg     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Tg(ML5sHEL)5Ccg/0

        C57BL/6-Tg(ML5sHEL)5Ccg
  • immune system phenotype
  • abnormal B cell anergy
    • abnormally low levels of anti-hen egg lysozyme (HEL) antibodies are made in response to immunization with HEL   (MGI Ref ID J:78308)
    • 50-fold lower levels of anti-HEL antibodies occur in response to immunization with HEL coupled with sheep red blood cells, which is a T cell-independent method of activating B cells   (MGI Ref ID J:78308)
  • homeostasis/metabolism phenotype
  • abnormal circulating protein level
    • hen egg lysozyme (HEL) is found in circulation at a median level of 17.3 ng ml-1   (MGI Ref ID J:78308)

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Tg(ML5sHEL)5Ccg/0

        involves: C57BL/6 * CBA
  • immune system phenotype
  • abnormal B cell anergy
    • abnormally low levels of anti-hen egg lysozyme (HEL) antibodies are made in response to immunization with HEL   (MGI Ref ID J:78308)
  • abnormal T cell anergy
    • T cell response to HEL antigen in vitro is much lower than T cells from non-transgenic controls   (MGI Ref ID J:78308)

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(ML5sHEL)5Ccg
Allele Name transgene insertion 5, Christopher C Goodnow
Allele Type Transgenic (random, expressed)
Common Name(s) MD5; ML-5; ML5; sHEL; solHEL;
Mutation Made By Christopher Goodnow,   Stanford University School of Medicine
Strain of OriginC57BL/6
Expressed Gene HEL, HEL, chicken
Promoter Mt1, metallothionein 1, mouse, laboratory
Molecular Note A genomic fragment containing the coding exons of the chicken lysozyme gene (also known as hen egg lysozyme, HEL) was linked to a mouse metallothionein I promoter. The mouse metallothionein I promoter is active during embryonic, fetal, and adult life, and can be induced to higher levels of transcription by heavy metals. Mice carrying the transgene had measurable, soluble chicken lysozyme in their serum. The line chosen for study (ML-5) had the highest serum lysozyme concentrations. [MGI Ref ID J:78308]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(KLK4mHEL)6Ccg, Tg(ML5sHEL)5Ccg, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Goodnow CC; Crosbie J; Adelstein S; Lavoie TB; Smith-Gill SJ; Brink RA; Pritchard-Briscoe H; Wotherspoon JS; Loblay RH; Raphael K; et al.. 1988. Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature 334(6184):676-82. [PubMed: 3261841]  [MGI Ref ID J:78308]

Additional References

Tg(ML5sHEL)5Ccg related

Akkaraju S; Ho WY; Leong D; Canaan K; Davis MM; Goodnow CC. 1997. A range of CD4 T cell tolerance: partial inactivation to organ-specific antigen allows nondestructive thyroiditis or insulitis. Immunity 7(2):255-71. [PubMed: 9285410]  [MGI Ref ID J:78309]

Barrington RA; Borde M; Rao A; Carroll MC. 2006. Involvement of NFAT1 in B cell self-tolerance. J Immunol 177(3):1510-5. [PubMed: 16849457]  [MGI Ref ID J:137979]

Blery M; Tze L; Miosge LA; Jun JE; Goodnow CC. 2006. Essential role of membrane cholesterol in accelerated BCR internalization and uncoupling from NF-kappa B in B cell clonal anergy. J Exp Med 203(7):1773-83. [PubMed: 16801401]  [MGI Ref ID J:124402]

Browne CD; Del Nagro CJ; Cato MH; Dengler HS; Rickert RC. 2009. Suppression of phosphatidylinositol 3,4,5-trisphosphate production is a key determinant of B cell anergy. Immunity 31(5):749-60. [PubMed: 19896393]  [MGI Ref ID J:155314]

Calderon B; Suri A; Miller MJ; Unanue ER. 2008. Dendritic cells in islets of Langerhans constitutively present beta cell-derived peptides bound to their class II MHC molecules. Proc Natl Acad Sci U S A 105(16):6121-6. [PubMed: 18427107]  [MGI Ref ID J:134675]

Chackerian B; Durfee MR; Schiller JT. 2008. Virus-like display of a neo-self antigen reverses B cell anergy in a B cell receptor transgenic mouse model. J Immunol 180(9):5816-25. [PubMed: 18424700]  [MGI Ref ID J:134321]

Chang NH; Cheung YH; Loh C; Pau E; Roy V; Cai YC; Wither J. 2010. B cell activating factor (BAFF) and T cells cooperate to breach B cell tolerance in lupus-prone New Zealand Black (NZB) mice. PLoS One 5(7):e11691. [PubMed: 20661465]  [MGI Ref ID J:163088]

Cook MC; Basten A; Fazekas de St Groth B. 1997. Outer periarteriolar lymphoid sheath arrest and subsequent differentiation of both naive and tolerant immunoglobulin transgenic B cells is determined by B cell receptor occupancy. J Exp Med 186(5):631-43. [PubMed: 9271579]  [MGI Ref ID J:132748]

Cornall RJ; Cheng AM; Pawson T; Goodnow CC. 2000. Role of Syk in B-cell development and antigen-receptor signaling. Proc Natl Acad Sci U S A 97(4):1713-8. [PubMed: 10677523]  [MGI Ref ID J:60647]

Cornall RJ; Cyster JG; Hibbs ML; Dunn AR; Otipoby KL; Clark EA; Goodnow CC. 1998. Polygenic autoimmune traits: Lyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection. Immunity 8(4):497-508. [PubMed: 9586639]  [MGI Ref ID J:110531]

Cox SL; Stolp J; Hallahan NL; Counotte J; Zhang W; Serreze DV; Basten A; Silveira PA. 2010. Enhanced responsiveness to T-cell help causes loss of B-lymphocyte tolerance to a beta-cell neo-self-antigen in type 1 diabetes prone NOD mice. Eur J Immunol 40(12):3413-25. [PubMed: 21108464]  [MGI Ref ID J:174579]

Culton DA; O'Conner BP; Conway KL; Diz R; Rutan J; Vilen BJ; Clarke SH. 2006. Early preplasma cells define a tolerance checkpoint for autoreactive B cells. J Immunol 176(2):790-802. [PubMed: 16393962]  [MGI Ref ID J:126633]

Cyster JG; Goodnow CC. 1995. Protein tyrosine phosphatase 1C negatively regulates antigen receptor signaling in B lymphocytes and determines thresholds for negative selection. Immunity 2(1):13-24. [PubMed: 7600299]  [MGI Ref ID J:28348]

Ekland EH; Forster R; Lipp M; Cyster JG. 2004. Requirements for follicular exclusion and competitive elimination of autoantigen-binding B cells. J Immunol 172(8):4700-8. [PubMed: 15067045]  [MGI Ref ID J:89130]

Enders A; Bouillet P; Puthalakath H; Xu Y; Tarlinton DM; Strasser A. 2003. Loss of the pro-apoptotic BH3-only Bcl-2 family member Bim inhibits BCR stimulation-induced apoptosis and deletion of autoreactive B cells. J Exp Med 198(7):1119-26. [PubMed: 14517273]  [MGI Ref ID J:86002]

Foote LC; Evans JW; Cifuni JM; Siracusa MC; Monteforte GM; McCole JL; D'Orazio CC; Hastings WD; Rothstein TL. 2004. Interleukin-4 produces a breakdown of tolerance in vivo with autoantibody formation and tissue damage. Autoimmunity 37(8):569-77. [PubMed: 15763919]  [MGI Ref ID J:128253]

Giltiay NV; Lu Y; Allman D; Jorgensen TN; Li X. 2010. The adaptor molecule Act1 regulates BAFF responsiveness and self-reactive B cell selection during transitional B cell maturation. J Immunol 185(1):99-109. [PubMed: 20543113]  [MGI Ref ID J:161592]

Hartley SB; Crosbie J; Brink R; Kantor AB; Basten A; Goodnow CC. 1991. Elimination from peripheral lymphoid tissues of self-reactive B lymphocytes recognizing membrane-bound antigens. Nature 353(6346):765-9. [PubMed: 1944535]  [MGI Ref ID J:78307]

Hermiston ML; Tan AL; Gupta VA; Majeti R; Weiss A. 2005. The juxtamembrane wedge negatively regulates CD45 function in B cells. Immunity 23(6):635-47. [PubMed: 16356861]  [MGI Ref ID J:113310]

Hippen KL; Schram BR; Tze LE; Pape KA; Jenkins MK; Behrens TW. 2005. In vivo assessment of the relative contributions of deletion, anergy, and editing to B cell self-tolerance. J Immunol 175(2):909-16. [PubMed: 16002689]  [MGI Ref ID J:100671]

Hippen KL; Tze LE; Behrens TW. 2000. CD5 maintains tolerance in anergic B cells. J Exp Med 191(5):883-90. [PubMed: 10704468]  [MGI Ref ID J:124695]

Ho WY; Cooke MP; Goodnow CC; Davis MM. 1994. Resting and anergic B cells are defective in CD28-dependent costimulation of naive CD4+ T cells. J Exp Med 179(5):1539-49. [PubMed: 7909325]  [MGI Ref ID J:73608]

Ismail N; Basten A; Briscoe H; Bretscher PA. 2005. Increasing the foreignness of an antigen, by coupling a second and foreign antigen to it, increases the T helper type 2 component of the immune response to the first antigen. Immunology 115(1):34-41. [PubMed: 15819695]  [MGI Ref ID J:97463]

Kilmon MA; Rutan JA; Clarke SH; Vilen BJ. 2005. Low-affinity, Smith antigen-specific B cells are tolerized by dendritic cells and macrophages. J Immunol 175(1):37-41. [PubMed: 15972629]  [MGI Ref ID J:100598]

Kilmon MA; Wagner NJ; Garland AL; Lin L; Aviszus K; Wysocki LJ; Vilen BJ. 2007. Macrophages prevent the differentiation of autoreactive B cells by secreting CD40 ligand and interleukin-6. Blood 110(5):1595-602. [PubMed: 17712049]  [MGI Ref ID J:145511]

Kitaura Y; Jang IK; Wang Y; Han YC; Inazu T; Cadera EJ; Schlissel M; Hardy RR; Gu H. 2007. Control of the B cell-intrinsic tolerance programs by ubiquitin ligases Cbl and Cbl-b. Immunity 26(5):567-78. [PubMed: 17493844]  [MGI Ref ID J:123596]

Kumar KR; Li L; Yan M; Bhaskarabhatla M; Mobley AB; Nguyen C; Mooney JM; Schatzle JD; Wakeland EK; Mohan C. 2006. Regulation of B cell tolerance by the lupus susceptibility gene Ly108. Science 312(5780):1665-9. [PubMed: 16778059]  [MGI Ref ID J:109640]

Liu X; Wysocki LJ; Manser T. 2007. Autoantigen-B cell antigen receptor interactions that regulate expression of B cell antigen receptor Loci. J Immunol 178(8):5035-47. [PubMed: 17404286]  [MGI Ref ID J:145282]

Manderson AP; Quah B; Botto M; Goodnow CC; Walport MJ; Parish CR. 2006. A novel mechanism for complement activation at the surface of B cells following antigen binding. J Immunol 177(8):5155-62. [PubMed: 17015700]  [MGI Ref ID J:139451]

Mason DY; Jones M; Goodnow CC. 1992. Development and follicular localization of tolerant B lymphocytes in lysozyme/anti-lysozyme IgM/IgD transgenic mice. Int Immunol 4(2):163-75. [PubMed: 1622894]  [MGI Ref ID J:109923]

Mecklenbrauker I; Saijo K; Zheng NY; Leitges M; Tarakhovsky A. 2002. Protein kinase Cdelta controls self-antigen-induced B-cell tolerance. Nature 416(6883):860-5. [PubMed: 11976686]  [MGI Ref ID J:76134]

Miller AT; Beisner DR; Liu D; Cooke MP. 2009. Inositol 1,4,5-trisphosphate 3-kinase B is a negative regulator of BCR signaling that controls B cell selection and tolerance induction. J Immunol 182(8):4696-704. [PubMed: 19342645]  [MGI Ref ID J:147739]

Neighbors M; Hartley SB; Xu X; Castro AG; Bouley DM; O'Garra A. 2006. Breakpoints in immunoregulation required for Th1 cells to induce diabetes. Eur J Immunol 36(9):2315-23. [PubMed: 16933361]  [MGI Ref ID J:116743]

Nijnik A; Ferry H; Lewis G; Rapsomaniki E; Leung JC; Daser A; Lambe T; Goodnow CC; Cornall RJ. 2006. Spontaneous B cell hyperactivity in autoimmune-prone MRL mice. Int Immunol 18(7):1127-37. [PubMed: 16735376]  [MGI Ref ID J:110236]

O'Neill SK; Getahun A; Gauld SB; Merrell KT; Tamir I; Smith MJ; Dal Porto JM; Li QZ; Cambier JC. 2011. Monophosphorylation of CD79a and CD79b ITAM Motifs Initiates a SHIP-1 Phosphatase-Mediated Inhibitory Signaling Cascade Required for B Cell Anergy. Immunity 35(5):746-56. [PubMed: 22078222]  [MGI Ref ID J:178833]

Phan TG; Amesbury M; Gardam S; Crosbie J; Hasbold J; Hodgkin PD; Basten A; Brink R. 2003. B cell receptor-independent stimuli trigger immunoglobulin (Ig) class switch recombination and production of IgG autoantibodies by anergic self-reactive B cells. J Exp Med 197(7):845-60. [PubMed: 12668643]  [MGI Ref ID J:132538]

Refaeli Y; Young RM; Turner BC; Duda J; Field KA; Bishop JM. 2008. The B cell antigen receptor and overexpression of MYC can cooperate in the genesis of B cell lymphomas. PLoS Biol 6(6):e152. [PubMed: 18578569]  [MGI Ref ID J:139351]

Rodriguez-Pinto D; Moreno J. 2005. B cells can prime naive CD4+ T cells in vivo in the absence of other professional antigen-presenting cells in a CD154-CD40-dependent manner. Eur J Immunol 35(4):1097-105. [PubMed: 15756646]  [MGI Ref ID J:97821]

Roy V; Chang NH; Cai Y; Bonventi G; Wither J. 2005. Aberrant IgM signaling promotes survival of transitional T1 B cells and prevents tolerance induction in lupus-prone New Zealand black mice. J Immunol 175(11):7363-71. [PubMed: 16301643]  [MGI Ref ID J:122135]

Silveira PA; Chapman HD; Stolp J; Johnson E; Cox SL; Hunter K; Wicker LS; Serreze DV. 2006. Genes within the Idd5 and Idd9/11 Diabetes Susceptibility Loci Affect the Pathogenic Activity of B Cells in Nonobese Diabetic Mice. J Immunol 177(10):7033-41. [PubMed: 17082619]  [MGI Ref ID J:114754]

Silveira PA; Dombrowsky J; Johnson E; Chapman HD; Nemazee D; Serreze DV. 2004. B cell selection defects underlie the development of diabetogenic APCs in nonobese diabetic mice. J Immunol 172(8):5086-94. [PubMed: 15067092]  [MGI Ref ID J:89156]

Van Parijs L; Biuckians A; Abbas AK. 1998. Functional roles of Fas and Bcl-2-regulated apoptosis of T lymphocytes. J Immunol 160(5):2065-71. [PubMed: 9498742]  [MGI Ref ID J:112062]

Winslow MM; Gallo EM; Neilson JR; Crabtree GR. 2006. The calcineurin phosphatase complex modulates immunogenic B cell responses. Immunity 24(2):141-52. [PubMed: 16473827]  [MGI Ref ID J:113318]

Wong MX; Hayball JD; Jackson DE. 2008. PECAM-1-regulated signalling thresholds control tolerance in anergic transgenic B-cells. Mol Immunol 45(6):1767-81. [PubMed: 17977600]  [MGI Ref ID J:131644]

Young RM; Hardy IR; Clarke RL; Lundy N; Pine P; Turner BC; Potter TA; Refaeli Y. 2009. Mouse models of non-Hodgkin lymphoma reveal Syk as an important therapeutic target. Blood 113(11):2508-16. [PubMed: 18981293]  [MGI Ref ID J:146340]

Young RM; Polsky A; Refaeli Y. 2009. TC-PTP is required for the maintenance of MYC-driven B-cell lymphomas. Blood 114(24):5016-23. [PubMed: 19755676]  [MGI Ref ID J:155497]

Zwickey HL; Unternaehrer JJ; Mellman I. 2006. Presentation of self-antigens on MHC class II molecules during dendritic cell maturation. Int Immunol 18(1):199-209. [PubMed: 16361313]  [MGI Ref ID J:104201]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing
Order this mouse

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $1980.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

  • Cryorecovery - Standard.
    We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing
Order this mouse

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2574.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

  • Cryorecovery - Standard.
    We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

General Supply Notes

  • This strain is included in the Induced Mutant Resource Colony collection.
  • Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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