Strain Name:

B6;129-Ltbtm1Flv/J

Stock Number:

003530

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Availability:

Cryopreserved - Ready for recovery

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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

Former Names B6,129-Ltbtm1Flv    (Changed: 15-DEC-04 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating InvestigatorDr. Richard A. Flavell,   Yale University School of Medicine

Description
The Ltb (lymphotoxin-beta) -deficient mice lack Peyer's patches, peripheral lymph nodes, splenic germinal centers and follicular dendritic cells. Note that this strain does have cervical and mesenteric lymph nodes, unlike Lta deficient mice. Mesenteric lymph nodes of Ltb deficient mice contain germinal center-like regions, but these areas appear to lack follicular dendritic cells. Homozygotes are viable and fertile.

Control Information

  Control
   101045 B6129SF2/J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ltb
005108   B6.129P2-Ltb/Tnf/Ltatm1Dvk/J
005112   STOCK Ltb/Tnftm1.1Dvk/J
View Strains carrying other alleles of Ltb     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Ltbtm1Flv/Ltbtm1Flv

        involves: 129S1/Sv * C57BL/6J
  • mortality/aging
  • increased sensitivity to xenobiotic induced morbidity/mortality
    • increase in mortality following a single dose of N-methyl-N-nitrosourea (MNU) compared to similarly treated wild-type controls   (MGI Ref ID J:91927)
  • immune system phenotype
  • abnormal humoral immune response
    • in response to stimulation with sheep red blood cells (SRBC), mice fail to produce anti-SRBC IgG at day 6 and only produce a negligible amount by day 15 unlike wild-type mice   (MGI Ref ID J:39746)
    • while mice produce wild-type levels of anti-NP following stimulation with NP-CGG, mice only show low levels of affinity maturation   (MGI Ref ID J:39746)
    • decreased IgA level   (MGI Ref ID J:39746)
  • abnormal mesenteric lymph node morphology
    • mesenteric lymph nodes are smaller than in wild-type   (MGI Ref ID J:39746)
    • B cell area is larger than in wild-type   (MGI Ref ID J:39746)
  • abnormal spleen morphology
    • spleen architecture is disrupted and the spleen is disorganized   (MGI Ref ID J:39746)
    • abnormal spleen red pulp morphology
      • mice exhibit leukocyte invasion of red pulp   (MGI Ref ID J:39746)
    • abnormal spleen white pulp morphology   (MGI Ref ID J:39746)
  • absent Peyer's patches   (MGI Ref ID J:39746)
  • absent peripheral lymph nodes
    • peripheral lymph nodes are absent   (MGI Ref ID J:39746)
    • however, mesenteric and cervical lymph nodes are present   (MGI Ref ID J:39746)
  • hematopoietic system phenotype
  • abnormal spleen morphology
    • spleen architecture is disrupted and the spleen is disorganized   (MGI Ref ID J:39746)
    • abnormal spleen red pulp morphology
      • mice exhibit leukocyte invasion of red pulp   (MGI Ref ID J:39746)
    • abnormal spleen white pulp morphology   (MGI Ref ID J:39746)
  • decreased IgA level   (MGI Ref ID J:39746)
  • homeostasis/metabolism phenotype
  • increased sensitivity to xenobiotic induced morbidity/mortality
    • increase in mortality following a single dose of N-methyl-N-nitrosourea (MNU) compared to similarly treated wild-type controls   (MGI Ref ID J:91927)
View Research Applications

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

Ltbtm1Flv related

Developmental Biology Research
Internal/Organ Defects
      Lymphoid Tissue Defects

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
Lymphoid Tissue Defects
      selective lymph node development defects

Internal/Organ Research
Lymphoid Tissue Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ltbtm1Flv
Allele Name targeted mutation 1, Richard A Flavell
Allele Type Targeted (Null/Knockout)
Common Name(s) LT beta-; LTbeta-;
Mutation Made ByDr. Richard Flavell,   Yale University School of Medicine
Strain of Origin129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line NameW9.5/W95
ES Cell Line Strain129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name Ltb, lymphotoxin B
Chromosome 17
Gene Common Name(s) AI662801; LTbeta; TNFC; TNFSF3; Tnfc; expressed sequence AI662801; lymphotoxin beta; p33; tumor necrosis factor C;
Molecular Note A neomycin resistance cassette replaced a 0.7 kb fragment of the gene, truncating the coding sequence at codon 153. Northern blots of total RNA from splenocytes from homozygous mutant mice showed an absence of mRNA for the targeted gene. [MGI Ref ID J:39746] [MGI Ref ID J:95222]

Genotyping

Genotyping Information

Genotyping Protocols

Ltbtm1Flv, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Koni PA; Sacca R; Lawton P; Browning JL; Ruddle NH; Flavell RA. 1997. Distinct roles in lymphoid organogenesis for lymphotoxins alpha and beta revealed in lymphotoxin beta-deficient mice. Immunity 6(4):491-500. [PubMed: 9133428]  [MGI Ref ID J:39746]

Additional References

Ltbtm1Flv related

Bentley KL; Stranford S; Liao S; Mounzer RM; Ruddle FH; Ruddle NH. 2011. High endothelial venule reporter mice to probe regulation of lymph node vasculature. Adv Exp Med Biol 691:35-44. [PubMed: 21153307]  [MGI Ref ID J:197525]

Berger DP; Naniche D; Crowley MT; Koni PA; Flavell RA; Oldstone MB. 1999. Lymphotoxin-beta-deficient mice show defective antiviral immunity. Virology 260(1):136-47. [PubMed: 10405365]  [MGI Ref ID J:102625]

Browning JL; Allaire N; Ngam-Ek A; Notidis E; Hunt J; Perrin S; Fava RA. 2005. Lymphotoxin-beta receptor signaling is required for the homeostatic control of HEV differentiation and function. Immunity 23(5):539-50. [PubMed: 16286021]  [MGI Ref ID J:113284]

Drayton DL; Bonizzi G; Ying X; Liao S; Karin M; Ruddle NH. 2004. I kappa B kinase complex alpha kinase activity controls chemokine and high endothelial venule gene expression in lymph nodes and nasal-associated lymphoid tissue. J Immunol 173(10):6161-8. [PubMed: 15528353]  [MGI Ref ID J:94289]

Drayton DL; Ying X; Lee J; Lesslauer W; Ruddle NH. 2003. Ectopic LT alpha beta directs lymphoid organ neogenesis with concomitant expression of peripheral node addressin and a HEV-restricted sulfotransferase. J Exp Med 197(9):1153-63. [PubMed: 12732657]  [MGI Ref ID J:133242]

Ericsson A; Kotarsky K; Svensson M; Sigvardsson M; Agace W. 2006. Functional characterization of the CCL25 promoter in small intestinal epithelial cells suggests a regulatory role for caudal-related homeobox (Cdx) transcription factors. J Immunol 176(6):3642-51. [PubMed: 16517733]  [MGI Ref ID J:129504]

Finke D; Acha-Orbea H; Mattis A; Lipp M; Kraehenbuhl J. 2002. CD4+CD3- cells induce Peyer's patch development: role of alpha4beta1 integrin activation by CXCR5. Immunity 17(3):363-73. [PubMed: 12354388]  [MGI Ref ID J:111436]

Fletcher CA; Sutherland AP; Groom JR; Batten ML; Ng LG; Gommerman J; Mackay F. 2006. Development of nephritis but not sialadenitis in autoimmune-prone BAFF transgenic mice lacking marginal zone B cells. Eur J Immunol 36(9):2504-14. [PubMed: 16906535]  [MGI Ref ID J:116737]

Franki AS; Van Beneden K; Dewint P; Hammond KJ; Lambrecht S; Leclercq G; Kronenberg M; Deforce D; Elewaut D. 2006. A unique lymphotoxin {alpha}beta-dependent pathway regulates thymic emigration of V{alpha}14 invariant natural killer T cells. Proc Natl Acad Sci U S A 103(24):9160-5. [PubMed: 16751279]  [MGI Ref ID J:111050]

Fukuyama S; Hiroi T; Yokota Y; Rennert PD; Yanagita M; Kinoshita N; Terawaki S; Shikina T; Yamamoto M; Kurono Y; Kiyono H. 2002. Initiation of NALT organogenesis is independent of the IL-7R, LTbetaR, and NIK signaling pathways but requires the Id2 gene and CD3(-)CD4(+)CD45(+) cells. Immunity 17(1):31-40. [PubMed: 12150889]  [MGI Ref ID J:78101]

Koni PA; Flavell RA. 1998. A role for tumor necrosis factor receptor type 1 in gut-associated lymphoid tissue development: genetic evidence of synergism with lymphotoxin beta. J Exp Med 187(12):1977-83. [PubMed: 9625757]  [MGI Ref ID J:110881]

Koni PA; Flavell RA. 1999. Lymph node germinal centers form in the absence of follicular dendritic cell networks. J Exp Med 189(5):855-64. [PubMed: 10049949]  [MGI Ref ID J:111249]

Kranich J; Krautler NJ; Heinen E; Polymenidou M; Bridel C; Schildknecht A; Huber C; Kosco-Vilbois MH; Zinkernagel R; Miele G; Aguzzi A. 2008. Follicular dendritic cells control engulfment of apoptotic bodies by secreting Mfge8. J Exp Med 205(6):1293-302. [PubMed: 18490487]  [MGI Ref ID J:137077]

Kumar V; Scandella E; Danuser R; Onder L; Nitschke M; Fukui Y; Halin C; Ludewig B; Stein JV. 2010. Global lymphoid tissue remodeling during a viral infection is orchestrated by a B cell-lymphotoxin-dependent pathway. Blood 115(23):4725-33. [PubMed: 20185585]  [MGI Ref ID J:161566]

Kwa SF; Beverley P; Smith AL. 2006. Peyer's patches are required for the induction of rapid Th1 responses in the gut and mesenteric lymph nodes during an enteric infection. J Immunol 176(12):7533-41. [PubMed: 16751400]  [MGI Ref ID J:132354]

Liu J; Xiang Z; Ma X. 2004. Role of IFN regulatory factor-1 and IL-12 in immunological resistance to pathogenesis of N-methyl-N-nitrosourea-induced T lymphoma. J Immunol 173(2):1184-93. [PubMed: 15240709]  [MGI Ref ID J:91927]

Manuelidis L; Zaitsev I; Koni P; Yun Lu Z; Flavell RA; Fritch W. 2000. Follicular dendritic cells and dissemination of creutzfeldt-jakob disease J Virol 74(18):8614-22. [PubMed: 10954563]  [MGI Ref ID J:64034]

Mounzer RH; Svendsen OS; Baluk P; Bergman CM; Padera TP; Wiig H; Jain RK; McDonald DM; Ruddle NH. 2010. Lymphotoxin-alpha contributes to lymphangiogenesis. Blood 116(12):2173-82. [PubMed: 20566898]  [MGI Ref ID J:164499]

Oldstone MB; Race R; Thomas D; Lewicki H; Homann D; Smelt S; Holz A; Koni P; Lo D; Chesebro B; Flavell R. 2002. Lymphotoxin-alpha- and lymphotoxin-beta-deficient mice differ in susceptibility to scrapie: evidence against dendritic cell involvement in neuroinvasion. J Virol 76(9):4357-63. [PubMed: 11932402]  [MGI Ref ID J:126282]

Sacca R; Cuff CA; Lesslauer W; Ruddle NH. 1998. Differential activities of secreted lymphotoxin-alpha3 and membrane lymphotoxin-alpha1beta2 in lymphotoxin-induced inflammation: critical role of TNF receptor 1 signaling. J Immunol 160(1):485-91. [PubMed: 9552007]  [MGI Ref ID J:110950]

Soderberg KA; Linehan MM; Ruddle NH; Iwasaki A. 2004. MAdCAM-1 expressing sacral lymph node in the lymphotoxin beta-deficient mouse provides a site for immune generation following vaginal herpes simplex virus-2 infection. J Immunol 173(3):1908-13. [PubMed: 15265924]  [MGI Ref ID J:92085]

Spahn TW; Fontana A; Faria AM; Slavin AJ; Eugster HP; Zhang X; Koni PA; Ruddle NH; Flavell RA; Rennert PD; Weiner HL. 2001. Induction of oral tolerance to cellular immune responses in the absence of Peyer's patches. Eur J Immunol 31(4):1278-87. [PubMed: 11298355]  [MGI Ref ID J:119455]

Spahn TW; Maaser C; Eckmann L; Heidemann J; Lugering A; Newberry R; Domschke W; Herbst H; Kucharzik T. 2004. The lymphotoxin-beta receptor is critical for control of murine Citrobacter rodentium-induced colitis. Gastroenterology 127(5):1463-73. [PubMed: 15521015]  [MGI Ref ID J:93429]

Takebayashi K; Koboziev I; Ostanin DV; Gray L; Karlsson F; Robinson-Jackson SA; Kosloski-Davidson M; Dooley AB; Zhang S; Grisham MB. 2011. Role of the gut-associated and secondary lymphoid tissue in the induction of chronic colitis. Inflamm Bowel Dis 17(1):268-78. [PubMed: 20812332]  [MGI Ref ID J:175961]

Yang CY; Vogt TK; Favre S; Scarpellino L; Huang HY; Tacchini-Cottier F; Luther SA. 2014. Trapping of naive lymphocytes triggers rapid growth and remodeling of the fibroblast network in reactive murine lymph nodes. Proc Natl Acad Sci U S A 111(1):E109-18. [PubMed: 24367096]  [MGI Ref ID J:206381]

Ying X; Chan K; Shenoy P; Hill M; Ruddle NH. 2005. Lymphotoxin plays a crucial role in the development and function of nasal-associated lymphoid tissue through regulation of chemokines and peripheral node addressin. Am J Pathol 166(1):135-46. [PubMed: 15632007]  [MGI Ref ID J:95222]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
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 on the strain data sheet for further information.

Supply Notes

  • 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 View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
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 on the strain data sheet for further information.

Supply Notes

  • 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).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   101045 B6129SF2/J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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