Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain NOD/ShiLt Donor Strain C57BL/6J H2 Haplotype g7 Generation N11F15pN1
Donating Investigator Dr. David Serreze, The Jackson Laboratory
Related Genotype: A/A Tyrc/Tyrc
Transgenic mice are viable, fertile, normal in size, agouti in color and express a soluable form of hen egg lysozyme. They become diabetic at a rate similar to NOD controls. This strain can be used to study B-cell selection and tolerance as it relates to Type 1 Diabetes.
This transgenic strain was generated by backcrossing transgenic mice on the C57BL/6 background (Stock No. 002599) to NOD/ShiLt for 11 generations. The strain has been maintained subsequently by brother-sister matings. It has been observed that the agouti coat color co-segregates with the transgene; therefore, albino mice are likely to be wild-type and the agouti mice are likely to be transgenic. The Type 1 Diabetes Resource received this stock for Dr. David Serezze's research colony (Stock No. 004252) in 2007 at generation N11F15.
|Considerations for Choosing Controls|
Strains carrying Tg(ML5sHEL)5Ccg allele
002599 C57BL/6-Tg(ML5sHEL)5Ccg/JView Strains carrying Tg(ML5sHEL)5Ccg (1 strain)Strains carrying other alleles of Mt1
002211 129S7/SvEvBrd-Mt1tm1Bri Mt2tm1Bri/J 017833 B6.Cg-Tg(BCR/ABL)623Hkp/J 002210 B6.Cg-Tg(Mt1)174Bri/J 008850 B6;SJL-Tg(Mt1-LDLR)93-4Reh/AgnJ 003210 C57BL/6-Tg(Crh)227.1Pbl/J 002193 C57BL/6J-Tg(MTn-lacZ)204Bri/J 005967 C57BL/6J-Tg(Mt1-Tnfsf4)1Pgn/Pgn 005968 C57BL/6J-Tg(Mt1-Tnfsf4)2Pgn/Pgn 002028 D2.Cg-Tg(pHRD)1Ust/J 002421 FVB/N-Tg(MtTGFA)100Lmb/J 002675 FVB/N-Tg(MtTPRMET)243Lng/J 002775 FVB/N-Tg(MtTPRMET)773Lng/J 002209 STOCK Tg(Mt1)174Bri/J 002422 STOCK Tg(MtTGFA)42Lmb/J 003722 SW.Cg-Tg(MtTGFA)42Lmb/JView Strains carrying other alleles of Mt1 (15 strains)Strains carrying other alleles of HELView Strains carrying other alleles of HEL (4 strains)
View Research ApplicationsResearch ApplicationsThis mouse can be used to support research in many areas including:
Diabetes and Obesity Research
Type 1 Diabetes (IDDM) Analysis Strains
Immunology, Inflammation and Autoimmunity Research
Type 1 Diabetes
CD Antigens, Antigen Receptors, and Histocompatibility Markers
|Allele Name||transgene insertion 5, Christopher C Goodnow|
|Allele Type||Transgenic (Inserted expressed sequence)|
|Common Name(s)||MD5; ML-5; ML5; SWHEL; sHEL; solHEL;|
|Mutation Made By||Dr. Christopher Goodnow, Stanford University School of Medicine|
|Strain of Origin||C57BL/6JSfd|
|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]|
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]
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]
Baumjohann D; Preite S; Reboldi A; Ronchi F; Ansel KM; Lanzavecchia A; Sallusto F. 2013. Persistent antigen and germinal center B cells sustain T follicular helper cell responses and phenotype. Immunity 38(3):596-605. [PubMed: 23499493] [MGI Ref ID J:195114]
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]
Chung JY; Figgett W; Fairfax K; Bernard C; Chan J; Toh BH; Mackay F; Alderuccio F. 2014. Gene therapy delivery of myelin oligodendrocyte glycoprotein (MOG) via hematopoietic stem cell transfer induces MOG-specific B cell deletion. J Immunol 192(6):2593-601. [PubMed: 24532581] [MGI Ref ID J:209907]
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; 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]
Crawford G; Enders A; Gileadi U; Stankovic S; Zhang Q; Lambe T; Crockford TL; Lockstone HE; Freeman A; Arkwright PD; Smart JM; Ma CS; Tangye SG; Goodnow CC; Cerundolo V; Godfrey DI; Su HC; Randall KL; Cornall RJ. 2013. DOCK8 is critical for the survival and function of NKT cells. Blood 122(12):2052-61. [PubMed: 23929855] [MGI Ref ID J:202494]
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]
Getahun A; Smith MJ; Kogut I; van Dyk LF; Cambier JC. 2012. Retention of anergy and inhibition of antibody responses during acute gamma herpesvirus 68 infection. J Immunol 189(6):2965-74. [PubMed: 22904300] [MGI Ref ID J:189918]
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]
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]
Goodnow CC; Crosbie J; Adelstein S; Lavoie TB; Smith-Gill SJ; Mason DY; Jorgensen H; Brink RA; Pritchard-Briscoe H; Loughnan M; et al.. 1989. Clonal silencing of self-reactive B lymphocytes in a transgenic mouse model. Cold Spring Harb Symp Quant Biol 54 Pt 2:907-20. [PubMed: 2701221] [MGI Ref ID J:210801]
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]
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]
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]
Jeelall YS; Wang JQ; Law HD; Domaschenz H; Fung HK; Kallies A; Nutt SL; Goodnow CC; Horikawa K. 2012. Human lymphoma mutations reveal CARD11 as the switch between self-antigen-induced B cell death or proliferation and autoantibody production. J Exp Med 209(11):1907-17. [PubMed: 23027925] [MGI Ref ID J:190942]
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]
Lee SR; Rutan JA; Monteith AJ; Jones SZ; Kang SA; Krum KN; Kilmon MA; Roques JR; Wagner NJ; Clarke SH; Vilen BJ. 2012. Receptor cross-talk spatially restricts p-ERK during TLR4 stimulation of autoreactive B cells. J Immunol 189(8):3859-68. [PubMed: 22984080] [MGI Ref ID J:190650]
Limnander A; Zikherman J; Lau T; Leitges M; Weiss A; Roose JP. 2014. Protein kinase Cdelta promotes transitional B cell-negative selection and limits proximal B cell receptor signaling to enforce tolerance. Mol Cell Biol 34(8):1474-85. [PubMed: 24515435] [MGI Ref ID J:213625]
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]
Poe JC; Kountikov EI; Lykken JM; Natarajan A; Marchuk DA; Tedder TF. 2014. EndoU is a novel regulator of AICD during peripheral B cell selection. J Exp Med 211(1):57-69. [PubMed: 24344237] [MGI Ref ID J:208364]
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]
Yau IW; Cato MH; Jellusova J; Hurtado de Mendoza T; Brink R; Rickert RC. 2013. Censoring of self-reactive B cells by follicular dendritic cell-displayed self-antigen. J Immunol 191(3):1082-90. [PubMed: 23817432] [MGI Ref ID J:205710]
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]
Yu M; Chen Y; He Y; Podd A; Fu G; Wright JA; Kleiman E; Khan WN; Wen R; Wang D. 2012. Critical role of B cell lymphoma 10 in BAFF-regulated NF-kappaB activation and survival of anergic B cells. J Immunol 189(11):5185-93. [PubMed: 23087406] [MGI Ref ID J:190683]
Zikherman J; Doan K; Parameswaran R; Raschke W; Weiss A. 2012. Quantitative differences in CD45 expression unmask functions for CD45 in B-cell development, tolerance, and survival. Proc Natl Acad Sci U S A 109(1):E3-12. [PubMed: 22135465] [MGI Ref ID J:180527]
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]
Animal Health ReportsProduction of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
|Pricing for USA, Canada and Mexico shipping destinations|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2525.00
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.
Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. 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. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 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|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $3283.00
Cryorecovery - Standard.
Progeny testing is not required.
|Considerations for Choosing Controls|
|Control Pricing Information for Genetically Engineered Mutant Strains.|
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