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   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

      assigned by genotype

Rela^tm1Bal/Rela^tm1Bal

        involves: 129S4/SvJae * C57BL/6J

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

Rela^tm1Bal/Rela^tm1Bal

        B6;129S4-Rela^tm1Bal/J

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

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

Rela^tm1Bal/Rela^tm1Bal

        B6.129S4-Rela^tm1Bal

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

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

Allele Symbol		Relatm1Bal
Allele Name		targeted mutation 1, David Baltimore
Allele Type		Targeted (knock-out)
Common Name(s)		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)		MGC131774; NFKB3; NFkB; p65; p65 NF kappaB;
Molecular Note		The gene was disrupted using neomycin resistance cassette. The vector replaced sequences encoding most of exos 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), STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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]

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]

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]

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]

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]

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]

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]

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]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the 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 for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks. 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. 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
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

See Terms of Use

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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Ordering and Purchasing Information

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      JAX^® Mice Orders
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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

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.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.