Strain Data Sheet

RBRC02142

Strain Information

Image
BRC No.RBRC02142
TypeTargeted Mutation CongenicCartagena
SpeciesMus musculus
Strain nameB6.129S2-Pdcd1<tm1Hon>/HonRbrc
Former Common nameC57BL/6-PD-1KO, C57BL/6-Pdcd1-/- mouse
H-2 Haplotype
ES Cell lineD3 [129S2/SvPas]
Background strainC57BL/6
Appearanceblack [(a/a B/B C/C)]
Strain developmentDeveloped by Tasuku Honjo, Graduate School of Medicine, Kyoto University in 1998. The knockout construct was electoroporated into D3 ES cells derived from 129S2/SvPas. The mutant mice were backcrossed to C57BL/6 over 11 generations.
Strain descriptionPD1 knockout mice. EcoRV site of exon 3 to PvuII site of exon 5 was replaced with noemycin selection cassette. PD1 (Pdcd1, programmed cell death 1) gene is an immunoinhibitory receptor that belongs to the CD28 family, plays a role in the negative control of proliferation, differentiation and class switching of B cells. PD1 deficiency has been shown to develop different forms of autoimmune diseases on different backgrounds of mice. Homozygous PD1 mutant mice of C57BL/6 background show moderate but consistent splenomegaly, and spontaneously develop characteristic lupus-like proliferative arthritis and golmerulonephritis with the age.
Colony maintenanceHomozygote x Homozygote.
References
Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses.
H Nishimura, N Minato, T Nakano, T Honjo
Int. Immunol., 10, 1563-1572 (1998). 9796923

Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor.
H Nishimura, M Nose, H Hiai, N Minato, T Honjo
Immunity, 11, 141-151 (1999). 10485649

Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice.
H Nishimura, T Okazaki, Y Tanaka, K Nakatani, M Hara, A Matsumori, S Sasayama, A Mizoguchi, H Hiai, N Minato, T Honjo
Science, 291, 319-322 (2001). 11209085

Health Report

Examination Date / Room / Rack2025-08-18Room:3-3Rack:ASentinel mouse program
2025-06-09Room:3-3Rack:ASentinel mouse program
2025-03-10Room:3-3Rack:ASentinel mouse program
2024-12-09Room:3-3Rack:ASentinel mouse program

Gene

Gene SymbolGene NameChr.Allele SymbolAllele NameCommon NamesPromoterDiseases Related to This Gene
Pdcd1
MGI:104879		programmed cell death 11Pdcd1<tm1Hon>
MGI:2386184		targeted mutation 1, Tasuku Honjo
  • multiple sclerosis, susceptibility to(MedGEN)

  • systemic lupus erythematosus(DisGeNET)

  • systemic lupus erythematosus, susceptibility to, 2(MedGEN)
    • neo neomycin resistance gene (E. coli)1 mouse phosphoglycerate kinase promoter (PGK promoter)

    Phenotype

    Phenotype annotation from literatures by Mammalian phenotype ontology
  • abnormal T cell activation (MP:0001828)

  • abnormal cardiac muscle contractility (MP:0002972)

  • abnormal cardiac output (MP:0001627)

  • abnormal cardiovascular system physiology (MP:0001544)

  • abnormal heart morphology (MP:0000266)
    • more 28 phenotypes
  • abnormal immunoglobulin level (MP:0002490)

  • abnormal leukopoiesis (MP:0005460)

  • abnormal myelopoiesis (MP:0001601)

  • abnormal response to transplant (MP:0005671)

  • arthritis (MP:0002993)

  • cardiac fibrosis (MP:0003141)

  • decreased heart right ventricle wall thickness (MP:0021160)

  • dilated heart ventricle (MP:0008022)

  • enlarged heart (MP:0000274)

  • enlarged liver (MP:0000599)

  • enlarged spleen (MP:0000691)

  • exophthalmos (MP:0002750)

  • glomerulonephritis (MP:0002743)

  • hepatic necrosis (MP:0001654)

  • increased B cell number (MP:0005014)

  • increased B cell proliferation (MP:0005154)

  • increased B-1 B cell number (MP:0004977)

  • increased IgA level (MP:0002495)

  • increased IgG2b level (MP:0008501)

  • increased IgG3 level (MP:0008502)

  • increased IgM level (MP:0002494)

  • increased autoantibody level (MP:0003725)

  • increased inflammatory response (MP:0001846)

  • increased interferon-gamma secretion (MP:0008566)

  • increased lymphocyte cell number (MP:0005013)

  • pancreas necrosis (MP:0009148)

  • premature death (MP:0002083)

  • pulmonary necrosis (MP:0010857)
    • Detailed phenotype data

    Ordering Information

    Donor DNAmouse phosphoglycerate kinase promoter (PGK promoter), E. coli neo, mouse PD-1(immunoglobulin superfamily member) genomic DNA
    Research applicationImmunology and Inflammation Research
    Specific Term and ConditionsIn publishing the research results obtained by use of the BIOLOGICAL RESOURCE, a citation of the following literature(s) designated by the DEPOSITOR is requested. Science 291, 319-322 (2001). In publishing the research results to be obtained by use of the BIOLOGICAL RESOURCE, an acknowledgment to the DEPOSITOR is requested. The RECIPIENT shall use the BIOLOGICAL RESOURCE only for academic research for the purpose of publishing the research results. RECIPIENT shall notify the PROVIDER upon filing a patent application claiming modification of the BIOLOGICAL RESOURCE or method(s) of manufacture or use(s) of the BIOLOGICAL RESOURCE.
    DepositorTasuku Honjo (Kyoto University)
    Strain Statusan icon for Frozen embryosFrozen embryos
    an icon for Frozen spermFrozen sperm
    Strain AvailabilityRecovered litters from cryopreserved embryos (2 to 4 months)
    Cryopreserved sperm (within 1 month)
    Cryopreserved embryos (within 1 month)
    Additional Info.Necessary documents for ordering:
    1. Order form (Japanese / English)
    2. Category I MTA: MTA for distribution with RIKEN BRC (Japanese / English)
    3. Acceptance of responsibility for living modified organism (Japanese / English)
    Honjo Lab HP
    Genotyping protocol -PCR-
    Mouse of the Month Jul 2012

    BRC mice in Publications

    Ogishi M, Kitaoka K, Good-Jacobson KL, Rinchai D, Zhang B, Wang J, Gies V, Rao G, Nguyen T, Avery DT, Khan T, Smithmyer ME, Mackie J, Yang R, Arias AA, Asano T, Ponsin K, Chaldebas M, Zhang P, Peel JN, Bohlen J, Lévy R, Pelham SJ, Lei WT, Han JE, Fagniez I, Chrabieh M, Laine C, Langlais D, Gruber C, Al Ali F, Rahman M, Aytekin C, Benson B, Dufort MJ, Domingo-Vila C, Moriya K, Shlomchik M, Uzel G, Gray PE, Suan D, Preece K, Chua I, Okada S, Chikuma S, Kiyonari H, Tree TI, Bogunovic D, Gros P, Marr N, Speake C, Oram RA, Béziat V, Bustamante J, Abel L, Boisson B, Korganow AS, Ma CS, Johnson MB, Chamoto K, Boisson-Dupuis S, Honjo T, Casanova JL, Tangye SG.
    Impaired development of memory B cells and antibody responses in humans and mice deficient in PD-1 signaling.
    Immunity 57(12) 2790-2807.e15(2024) 39603236
    Akama Y, Park EJ, Satoh-Takayama N, Ito A, Kawamoto E, Gaowa A, Matsuo E, Oikawa S, Saito M, Inoue S, Akimoto T, Suzuki K, Shimaoka M.
    Roles of programmed death-1 and muscle innate lymphoid cell-derived interleukin 13 in sepsis-induced intensive care unit-acquired weakness.
    J Cachexia Sarcopenia Muscle (2024) 39016179
    Suzuki K, Tajima M, Tokumaru Y, Oshiro Y, Nagata S, Kamada H, Kihara M, Nakano K, Honjo T, Ohta A.
    Anti-PD-1 antibodies recognizing the membrane-proximal region are PD-1 agonists that can down-regulate inflammatory diseases.
    Sci Immunol 8(79) eadd4947(2023) 36638191
    Gao Y, Song B, Aoki S, Ito K.
    Conjugation of human serum albumin and flucloxacillin provokes specific immune response in HLA-B*57:01 transgenic mice.
    Immunol Lett 249 5-11(2022) 35963284
    Sakurai Y, Usui Y, Hattori T, Takeuchi M, Takayama K, Karasawa Y, Nishio Y, Yamakawa N, Saitoh D, Goto H, Ito M.
    Programmed Cell Death-1 Pathway Deficiency Enhances Autoimmunity Leading to Dacryoadenitis of Mice.
    Am J Pathol 191(6) 1077-1093(2021) 33705751
    Susukida T, Kuwahara S, Song B, Kazaoka A, Aoki S, Ito K.
    Regulation of the immune tolerance system determines the susceptibility to HLA-mediated abacavir-induced skin toxicity.
    Commun Biol 4(1) 1137(2021) 34584206
    Takehara T, Wakamatsu E, Machiyama H, Nishi W, Emoto K, Azuma M, Soejima K, Fukunaga K, Yokosuka T.
    PD-L2 suppresses T cell signaling via coinhibitory microcluster formation and SHP2 phosphatase recruitment.
    Commun Biol 4(1) 581(2021) 33990697
    Miyajima M, Zhang B, Sugiura Y, Sonomura K, Guerrini MM, Tsutsui Y, Maruya M, Vogelzang A, Chamoto K, Honda K, Hikida T, Ito S, Qin H, Sanuki R, Suzuki K, Furukawa T, Ishihama Y, Matsuda F, Suematsu M, Honjo T, Fagarasan S.
    Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior.
    Nat Immunol 18(12) 1342-1352(2017) 29058703
    Karunarathne DS, Horne-Debets JM, Huang JX, Faleiro R, Leow CY, Amante F, Watkins TS, Miles JJ, Dwyer PJ, Stacey KJ, Yarski M, Poh CM, Lee JS, Cooper MA, Rénia L, Richard D, McCarthy JS, Sharpe AH, Wykes MN.
    Programmed Death-1 Ligand 2-Mediated Regulation of the PD-L1 to PD-1 Axis Is Essential for Establishing CD4(+) T Cell Immunity.
    Immunity 45(2) 333-45(2016) 27533014
    Okamura T, Sumitomo S, Morita K, Iwasaki Y, Inoue M, Nakachi S, Komai T, Shoda H, Miyazaki J, Fujio K, Yamamoto K.
    TGF-β3-expressing CD4+CD25(-)LAG3+ regulatory T cells control humoral immune responses.
    Nat Commun 6 6329(2015) 25695838
    Horne-Debets JM, Faleiro R, Karunarathne DS, Liu XQ, Lineburg KE, Poh CM, Grotenbreg GM, Hill GR, MacDonald KP, Good MF, Renia L, Ahmed R, Sharpe AH, Wykes MN.
    PD-1 dependent exhaustion of CD8+ T cells drives chronic malaria.
    Cell Rep 5(5) 1204-13(2013) 24316071
    Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, Hashimoto-Tane A, Azuma M, Saito T.
    Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2.
    J Exp Med 209(6) 1201-17(2012) 22641383
    Kawamoto S, Tran TH, Maruya M, Suzuki K, Doi Y, Tsutsui Y, Kato LM, Fagarasan S.
    The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut.
    Science 336(6080) 485-9(2012) 22539724
    Mumprecht S, Schürch C, Schwaller J, Solenthaler M, Ochsenbein AF.
    Programmed death 1 signaling on chronic myeloid leukemia-specific T cells results in T-cell exhaustion and disease progression.
    Blood 114(8) 1528-36(2009) 19420358