Strain Name:

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

Stock Number:

002599

Availability:

Repository-Cryopreserved

Description

Strain Information

Type Mutant Strain; Transgenic;
Additional information on Genetically Engineered Mutant Mice.
Specieslaboratory mouse
GenerationF?+10N1p (16-JAN-05)
 
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
004252   NOD.B6-Tg(ML5sHEL)5Ccg/Dvs
006610   NOD.B6-Tg(ML5sHEL)5Ccg/DvsJ
View Strains carrying   Tg(ML5sHEL)5Ccg     (2 strains)

View Strains carrying other alleles of Mt1     (12 strains)

Strains carrying other alleles of HEL
002598   C57BL/6-Tg(KLK4mHEL)6Ccg/J
004258   NOD.B6-Tg(KLK4mHEL)6Ccg/Dvs
View Strains carrying other alleles of HEL     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Tg(ML5sHEL)5Ccg/0

        C57BL/6-Tg(ML5sHEL)5Ccg
  • immune system phenotype
  • abnormal B cell anergy (MGI Ref ID J:78308)
    • abnormally low levels of anti-hen egg lysozyme (HEL) antibodies are made in response to immunization with HEL
    • 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
  • homeostasis/metabolism phenotype
  • abnormal circulating protein level (MGI Ref ID J:78308)
    • hen egg lysozyme (HEL) is found in circulation at a median level of 17.3 ng ml-1

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 (MGI Ref ID J:78308)
    • abnormally low levels of anti-hen egg lysozyme (HEL) antibodies are made in response to immunization with HEL
  • abnormal T cell anergy (MGI Ref ID J:78308)
    • T cell response to HEL antigen in vitro is much lower than T cells from non-transgenic controls
View Research Applications

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

Mt1 related

Metabolism Research

HEL related

Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers

Genes & Alleles

Gene & Allele Information

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, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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]

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]

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]

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]

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]

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]

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]

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]

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]

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

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $1900.00
*Price(s) in US dollars ($)

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $2470.00
*Price(s) in US dollars ($)

Additional Supply Details

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryorecovery - Standard.
    The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845.

  • This strain is included in the Induced Mutant Resource Colony collection.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
  International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions


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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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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use


General Terms and Conditions


Contact information

General inquiries

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phone:207-288-6470
fax:207-288-6655

JAX® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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