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 Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N3 Generation Definitions   Donating Investigator David Baltimore,   California Institute of Technology

Appearance
white-bellied agouti
Related Genotype: A^w/?

black
Related Genotype: a/a

Description
Mice homozygous for the Rela^tm1Bal targeted mutation die at embryonic day 14 from hepatocyte apoptosis and failure of hematopoiesis

Control Information

	Control
	Wild-type from the colony
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Rela^tm1Bal/Rela^tm1Bal

        involves: 129S4/SvJae * C57BL/6J

• mortality/aging
• complete lethality throughout fetal growth and development
  • after E14 mice begin to die and none survive to birth   (MGI Ref ID J:28390)
• liver/biliary system phenotype
• increased hepatocyte apoptosis
  • liver degeneration is associated with increased apoptosis of liver cells   (MGI Ref ID J:28390)
• liver degeneration
  • E15 to E16, mice exhibit liver degeneration that specifically targets hepatocytes leaving hematopoietic precursors and red blood cells intact   (MGI Ref ID J:28390)
  • liver degeneration is associated with increased apoptosis of liver cells   (MGI Ref ID J:28390)
• cardiovascular system phenotype
• internal hemorrhage
  • at E16, surviving mice exhibit massive abdominal hemorrhage   (MGI Ref ID J:28390)
• cellular phenotype
• increased hepatocyte apoptosis
  • liver degeneration is associated with increased apoptosis of liver cells   (MGI Ref ID J:28390)

Rela^tm1Bal/Rela^tm1Bal

        B6;129S4-Rela^tm1Bal/J

• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype
  • despite altered expression of Trp53, neurons exhibit normal camptothecin-induced neuronal death   (MGI Ref ID J:91366)

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

Rela^tm1Bal/Rela^tm1Bal

        involves: 129S4/SvJae

• nervous system phenotype
• abnormal neuron physiology
  • survival following treatment of sensory neurons with NGF is lower than for similarly treated wild-type neurons due to increased apoptosis   (MGI Ref ID J:119844)
  • however, sensory neurons exhibit normal survival response to BDNF   (MGI Ref ID J:119844)
• • increased neuron apoptosis
    • apoptosis in the trigeminal ganglia of E14 mice is increased compared to in wild-type mice   (MGI Ref ID J:119844)
• abnormal trigeminal nerve morphology
  • at E14, the number of neurons in the trigeminal ganglia is decrease compared to in wild-type mice   (MGI Ref ID J:119844)
• cellular phenotype
• abnormal cell death
  • embryonic fibroblasts treated with mTNF-alpha exhibit decreased survival compared to similarly treated cells   (MGI Ref ID J:28390)
• • increased neuron apoptosis
    • apoptosis in the trigeminal ganglia of E14 mice is increased compared to in wild-type mice   (MGI Ref ID J:119844)
• immune system phenotype
• *normal* immune system phenotype
  • mice exhibit normal dendritic cell development and maturation   (MGI Ref ID J:113514)
• • decreased marginal zone B cell number
    • when cells are used to reconstitute a Rag2 null mouse, the number of marginal zone B cells is reduced to one third of normal   (MGI Ref ID J:65246)
• hematopoietic system phenotype
• decreased marginal zone B cell number
  • when cells are used to reconstitute a Rag2 null mouse, the number of marginal zone B cells is reduced to one third of normal   (MGI Ref ID J:65246)

Rela^tm1Bal/Rela^tm1Bal

        B6.129S4-Rela^tm1Bal

• mortality/aging
• complete lethality throughout fetal growth and development
  • despite normal appearance up to E13, all mice are dead by E15   (MGI Ref ID J:111325)
• liver/biliary system phenotype
• increased hepatocyte apoptosis
  • most mice exhibit fetal liver cell apoptosis by E14.5   (MGI Ref ID J:111325)
• cardiovascular system phenotype
• internal hemorrhage
  • most mice exhibit abdominal hemorrhage by E14.5   (MGI Ref ID J:111325)
• cellular phenotype
• increased hepatocyte apoptosis
  • most mice exhibit fetal liver cell apoptosis by E14.5   (MGI Ref ID J:111325)

View Research Applications

Research Applications

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

Rela^tm1Bal related

Cancer Research
Oncogenes

Developmental Biology Research
Internal/Organ Defects
      liver

Internal/Organ Research
Liver Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Relatm1Bal
Allele Name		targeted mutation 1, David Baltimore
Allele Type		Targeted (knock-out)
Common Name(s)		Nfkb1tmBal; p65-; rela-;
Mutation Made By		David Baltimore,   California Institute of Technology
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Rela, v-rel reticuloendotheliosis viral oncogene homolog A (avian)
Chromosome		19
Gene Common Name(s)		NFKB3; NFkB; p65; p65 NF kappaB;
Molecular Note		The gene was disrupted using neomycin resistance cassette. The vector replaced sequences encoding most of exons 6, 8 and the entire exon 7. Protein was not detectable by Western analysis in embryonic fibroblast extracts from homozygous mutant animals. [MGI Ref ID J:28390]

Genotyping

Genotyping Information

Genotyping Protocols

NEOTD (Generic Neo), Standard PCR
Rela^tm1Bal, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Beg AA; Sha WC; Bronson RT; Ghosh S; Baltimore D. 1995. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B. Nature 376(6536):167-70. [PubMed: 7603567]  [MGI Ref ID J:28390]

Additional References

Rela^tm1Bal related

Alcamo E; Hacohen N; Schulte LC; Rennert PD; Hynes RO; Baltimore D. 2002. Requirement for the NF-kappaB family member RelA in the development of secondary lymphoid organs. J Exp Med 195(2):233-44. [PubMed: 11805150]  [MGI Ref ID J:76222]

Alcamo E; Mizgerd JP; Horwitz BH; Bronson R; Beg AA; Scott M; Doerschuk CM; Hynes RO; Baltimore D. 2001. Targeted mutation of TNF receptor I rescues the RelA-deficient mouse and reveals a critical role for NF-kappa B in leukocyte recruitment. J Immunol 167(3):1592-600. [PubMed: 11466381]  [MGI Ref ID J:84897]

Aleyasin H; Cregan SP; Iyirhiaro G; O'Hare MJ; Callaghan SM; Slack RS; Park DS. 2004. Nuclear factor-(kappa)B modulates the p53 response in neurons exposed to DNA damage. J Neurosci 24(12):2963-73. [PubMed: 15044535]  [MGI Ref ID J:90221]

Beg AA; Baltimore D. 1996. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death [see comments] Science 274(5288):782-4. [PubMed: 8864118]  [MGI Ref ID J:36492]

Boyle K; Azari MF; Cheema SS; Petratos S. 2005. TNFalpha mediates Schwann cell death by upregulating p75NTR expression without sustained activation of NFkappaB. Neurobiol Dis 20(2):412-27. [PubMed: 15905096]  [MGI Ref ID J:124444]

Cariappa A; Liou HC; Horwitz BH; Pillai S. 2000. Nuclear factor kappaB is required for the development of marginal zone B lymphocytes J Exp Med 192(8):1175-82. [PubMed: 11034607]  [MGI Ref ID J:65246]

Chen X; Ding WX; Ni HM; Gao W; Shi YH; Gambotto AA; Fan J; Beg AA; Yin XM. 2007. Bid-independent mitochondrial activation in tumor necrosis factor alpha-induced apoptosis and liver injury. Mol Cell Biol 27(2):541-53. [PubMed: 17101783]  [MGI Ref ID J:117693]

Dadgostar H; Zarnegar B; Hoffmann A; Qin XF; Truong U; Rao G; Baltimore D; Cheng G. 2002. Cooperation of multiple signaling pathways in CD40-regulated gene expression in B lymphocytes. Proc Natl Acad Sci U S A 99(3):1497-502. [PubMed: 11830667]  [MGI Ref ID J:126969]

Dahlman JM; Bakkar N; He W; Guttridge DC. 2010. NF-kappaB functions in stromal fibroblasts to regulate early postnatal muscle development. J Biol Chem 285(8):5479-87. [PubMed: 20018862]  [MGI Ref ID J:159757]

Delhase M; Kim SY; Lee H; Naiki-Ito A; Chen Y; Ahn ER; Murata K; Kim SJ; Lautsch N; Kobayashi KS; Shirai T; Karin M; Nakanishi M. 2011. TANK-binding kinase 1 (TBK1) controls cell survival through PAI-2/serpinB2 and transglutaminase 2. Proc Natl Acad Sci U S A :. [PubMed: 22203995]  [MGI Ref ID J:179973]

Demarchi F; Bertoli C; Greer PA; Schneider C. 2005. Ceramide triggers an NF-kappaB-dependent survival pathway through calpain. Cell Death Differ 12(5):512-22. [PubMed: 15933726]  [MGI Ref ID J:111869]

Erdman S; Fox JG; Dangler CA; Feldman D; Horwitz BH. 2001. Typhlocolitis in NF-kappa B-deficient mice. J Immunol 166(3):1443-7. [PubMed: 11160181]  [MGI Ref ID J:67107]

Gadjeva M; Tomczak MF; Zhang M; Wang YY; Dull K; Rogers AB; Erdman SE; Fox JG; Carroll M; Horwitz BH. 2004. A role for NF-kappaB subunits p50 and p65 in the inhibition of lipopolysaccharide-induced shock. J Immunol 173(9):5786-93. [PubMed: 15494531]  [MGI Ref ID J:93765]

Gadjeva M; Wang Y; Horwitz BH. 2007. NF-kappaB p50 and p65 subunits control intestinal homeostasis. Eur J Immunol 37(9):2509-17. [PubMed: 17705134]  [MGI Ref ID J:124335]

Grossmann M; Metcalf D; Merryfull J; Beg A; Baltimore D; Gerondakis S. 1999. The combined absence of the transcription factors Rel and RelA leads to multiple hemopoietic cell defects. Proc Natl Acad Sci U S A 96(21):11848-53. [PubMed: 10518539]  [MGI Ref ID J:111325]

Grumont R; Hochrein H; O'Keeffe M; Gugasyan R; White C; Caminschi I; Cook W; Gerondakis S. 2001. c-Rel Regulates Interleukin 12 p70 Expression in CD8(+) Dendritic Cells by Specifically Inducing p35 Gene Transcription. J Exp Med 194(8):1021-32. [PubMed: 11602633]  [MGI Ref ID J:72212]

Grumont R; Lock P; Mollinari M; Shannon FM; Moore A; Gerondakis S. 2004. The mitogen-induced increase in T cell size involves PKC and NFAT activation of Rel/NF-kappaB-dependent c-myc expression. Immunity 21(1):19-30. [PubMed: 15345217]  [MGI Ref ID J:93602]

Gugasyan R; Christou A; O'Reilly LA; Strasser A; Gerondakis S. 2006. Bcl-2 transgene expression fails to prevent fatal hepatocyte apoptosis induced by endogenous TNFalpha in mice lacking RelA. Cell Death Differ 13(7):1235-7. [PubMed: 16485035]  [MGI Ref ID J:126292]

Gugasyan R; Voss A; Varigos G; Thomas T; Grumont RJ; Kaur P; Grigoriadis G; Gerondakis S. 2004. The transcription factors c-rel and RelA control epidermal development and homeostasis in embryonic and adult skin via distinct mechanisms. Mol Cell Biol 24(13):5733-45. [PubMed: 15199130]  [MGI Ref ID J:91366]

Hamanoue M; Middleton G; Wyatt S; Jaffray E; Hay RT; Davies AM. 1999. p75-mediated NF-kappaB activation enhances the survival response of developing sensory neurons to nerve growth factor. Mol Cell Neurosci 14(1):28-40. [PubMed: 10433815]  [MGI Ref ID J:119844]

Isomura I; Palmer S; Grumont RJ; Bunting K; Hoyne G; Wilkinson N; Banerjee A; Proietto A; Gugasyan R; Li W; McNally A; Steptoe RJ; Thomas R; Shannon MF; Gerondakis S. 2009. c-Rel is required for the development of thymic Foxp3+ CD4 regulatory T cells. J Exp Med 206(13):3001-14. [PubMed: 19995950]  [MGI Ref ID J:155679]

Kaufmann T; Gugasyan R; Gerondakis S; Dixit VM; Strasser A. 2007. Loss of the BH3-only protein Bid does not rescue RelA-deficient embryos from TNF-R1-mediated fatal hepatocyte destruction. Cell Death Differ 14(3):637-9. [PubMed: 17096024]  [MGI Ref ID J:132334]

Kawahara TL; Michishita E; Adler AS; Damian M; Berber E; Lin M; McCord RA; Ongaigui KC; Boxer LD; Chang HY; Chua KF. 2009. SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span. Cell 136(1):62-74. [PubMed: 19135889]  [MGI Ref ID J:147591]

Lee KG; Xu S; Wong ET; Tergaonkar V; Lam KP. 2008. Bruton's tyrosine kinase separately regulates NFkappaB p65RelA activation and cytokine interleukin (IL)-10/IL-12 production in TLR9-stimulated B Cells. J Biol Chem 283(17):11189-98. [PubMed: 18276597]  [MGI Ref ID J:136576]

Liou HC; Hsia CY. 2003. Distinctions between c-Rel and other NF-kappaB proteins in immunity and disease. Bioessays 25(8):767-80. [PubMed: 12879447]  [MGI Ref ID J:84673]

Meffert MK; Chang JM; Wiltgen BJ; Fanselow MS; Baltimore D. 2003. NF-kappaB functions in synaptic signaling and behavior. Nat Neurosci 6(10):1072-8. [PubMed: 12947408]  [MGI Ref ID J:85743]

Nakamura-Yanagidaira T; Takahashi Y; Sano K; Murata T; Hayashi T. 2011. Development of spontaneous neuropathy in NF-kappaBp50-deficient mice by calcineurin-signal involving impaired NF-kappaB activation. Mol Vis 17:2157-70. [PubMed: 21850191]  [MGI Ref ID J:179520]

Ouaaz F; Arron J; Zheng Y; Choi Y; Beg AA. 2002. Dendritic cell development and survival require distinct NF-kappaB subunits. Immunity 16(2):257-70. [PubMed: 11869686]  [MGI Ref ID J:113514]

Quinton LJ; Jones MR; Simms BT; Kogan MS; Robson BE; Skerrett SJ; Mizgerd JP. 2007. Functions and regulation of NF-kappaB RelA during pneumococcal pneumonia. J Immunol 178(3):1896-903. [PubMed: 17237440]  [MGI Ref ID J:143632]

Rao S; Gerondakis S; Woltring D; Shannon MF. 2003. c-Rel is required for chromatin remodeling across the IL-2 gene promoter. J Immunol 170(7):3724-31. [PubMed: 12646638]  [MGI Ref ID J:125445]

Rosenfeld ME; Prichard L; Shiojiri N; Fausto N. 2000. Prevention of hepatic apoptosis and embryonic lethality in RelA/TNFR-1 double knockout mice. Am J Pathol 156(3):997-1007. [PubMed: 10702415]  [MGI Ref ID J:60742]

Ruan Q; Kameswaran V; Zhang Y; Zheng S; Sun J; Wang J; DeVirgiliis J; Liou HC; Beg AA; Chen YH. 2011. The Th17 immune response is controlled by the Rel-RORgamma-RORgamma T transcriptional axis. J Exp Med 208(11):2321-33. [PubMed: 22006976]  [MGI Ref ID J:178764]

Sheedy FJ; Palsson-McDermott E; Hennessy EJ; Martin C; O'Leary JJ; Ruan Q; Johnson DS; Chen Y; O'Neill LA. 2010. Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol 11(2):141-7. [PubMed: 19946272]  [MGI Ref ID J:158464]

Suzuki K; Murphy SH; Xia Y; Yokota M; Nakagomi D; Liu F; Verma IM; Nakajima H. 2011. Tumor suppressor p53 functions as a negative regulator in IgE-mediated mast cell activation. PLoS One 6(9):e25412. [PubMed: 21966524]  [MGI Ref ID J:177915]

Tomczak MF; Erdman SE; Davidson A; Wang YY; Nambiar PR; Rogers AB; Rickman B; Luchetti D; Fox JG; Horwitz BH. 2006. Inhibition of Helicobacter hepaticus-induced colitis by IL-10 requires the p50/p105 subunit of NF-kappa B. J Immunol 177(10):7332-9. [PubMed: 17082652]  [MGI Ref ID J:140612]

Vaira S; Alhawagri M; Anwisye I; Kitaura H; Faccio R; Novack DV. 2008. RelA/p65 promotes osteoclast differentiation by blocking a RANKL-induced apoptotic JNK pathway in mice. J Clin Invest 118(6):2088-97. [PubMed: 18464930]  [MGI Ref ID J:137682]

Wang J; Basagoudanavar SH; Wang X; Hopewell E; Albrecht R; Garcia-Sastre A; Balachandran S; Beg AA. 2010. NF-kappaB RelA subunit is crucial for early IFN-beta expression and resistance to RNA virus replication. J Immunol 185(3):1720-9. [PubMed: 20610653]  [MGI Ref ID J:162240]

Wang J; Wang X; Hussain S; Zheng Y; Sanjabi S; Ouaaz F; Beg AA. 2007. Distinct roles of different NF-kappa B subunits in regulating inflammatory and T cell stimulatory gene expression in dendritic cells. J Immunol 178(11):6777-88. [PubMed: 17513725]  [MGI Ref ID J:147847]

Zarnegar B; He JQ; Oganesyan G; Hoffmann A; Baltimore D; Cheng G. 2004. Unique CD40-mediated biological program in B cell activation requires both type 1 and type 2 NF-kappaB activation pathways. Proc Natl Acad Sci U S A 101(21):8108-13. [PubMed: 15148378]  [MGI Ref ID J:90663]

Zhang JY; Green CL; Tao S; Khavari PA. 2004. NF-kappaB RelA opposes epidermal proliferation driven by TNFR1 and JNK. Genes Dev 18(1):17-22. [PubMed: 14724177]  [MGI Ref ID J:119420]

Zhang JY; Tao S; Kimmel R; Khavari PA. 2005. CDK4 regulation by TNFR1 and JNK is required for NF-kappaB-mediated epidermal growth control. J Cell Biol 168(4):561-6. [PubMed: 15699216]  [MGI Ref ID J:129435]

von Vietinghoff S; Asagiri M; Azar D; Hoffmann A; Ley K. 2010. Defective regulation of CXCR2 facilitates neutrophil release from bone marrow causing spontaneous inflammation in severely NF-kappaB-deficient mice. J Immunol 185(1):670-8. [PubMed: 20519647]  [MGI Ref ID J:161430]

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

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
	Wild-type from the colony
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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The Jackson Laboratory's Genotype Promise

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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