NFκB-RE-luc

Random Transgenic

NFκB-RE-luc Random Transgenic Mouse Model

BALB/c Background

  • Model #
  • Genotype
  • Nomenclature
  • 10499-F
    tg/wt
    BALB/c-Tg(Rela-luc)31Xen
  • 10499-M
    tg/wt
    BALB/c-Tg(Rela-luc)31Xen
  • Carries a transgene containing 6 NFκB-responsive elements (RE) from the CMVα (immediate early) promoter placed upstream of a basal SV40 promoter, and a modified firefly luciferase cDNA (Promega pGL3)
  • Basal expression of the reporter is observed in the whole body
  • The reporter is inducible by LPS and TNFα
  • The model provides for the rapid study of transcriptional regulation of the NFκB gene
  • Useful in studying sepsis, arthritis, inflammatory bowel disease, apoptosis, tumor development, NFκB gene regulation, and the treatment of inflammatory diseases and cancer

Genetic Background:

BALB/c Background

Origin:

The NFκB-RE-luc mouse was developed by Caliper Life Sciences. The model was created by microinjecting a transgene containing 6 NFκB-responsive elements (RE) from the CMVα (immediate early) promoter placed upstream of a basal SV40 promoter, and a modified firefly luciferase cDNA (Promega pGL3). This transgene was microinjected into BALB/cJ zygotes. The resultant mice from founder line 31 were bred to BALB/cJ mice. Taconic received stock from Caliper in 2010, and the line was embryo transfer derived. In the production colony, the line is maintained by mating mice which are wild type to those which are hemizygous for the luciferase transgene.


Species:

Mouse

Initial Publication:

There is no specific publication describing the generation of these mice, but multiple publications exist demonstrating applications using this model and a similar model generated by Dr. Blomhoff. See reference list.

Other publications:

Carlsen H, Moskaug JØ, Fromm SH, Blomhoff R. (2002) In vivo imaging of NF-kappa B activity. J Immunol. 168(3):1441-6.

Døhlen G, Carlsen H, Blomhoff R, Thaulow E, Saugstad OD. (2005) Reoxygenation of hypoxic mice with 100% oxygen induces brain nuclear factor-kappa B. Pediatr Res. 58(5):941-5.

Alexander G, Carlsen H, Blomhoff R. (2006) Corneal NF-kappaB activity is necessary for the retention of transparency in the cornea of UV-B-exposed transgenic reporter mice. Exp Eye Res. 82(4):700-9.

Sadikot RT, Zeng H, Joo M, Everhart MB, Sherrill TP, Li B, Cheng DS, Yull FE, Christman JW, Blackwell TS. (2006) Targeted immunomodulation of the NF-kappaB pathway in airway epithelium impacts host defense against Pseudomonas aeruginosa. J Immunol. 176(8):4923-30.

Roth DJ, Jansen ED, Powers AC, Wang TG. (2006) A novel method of monitoring response to islet transplantation: bioluminescent imaging of an NF-κB transgenic mouse model. Transplantation. 81(8):1185-90.

Ho TY, Chen YS, Hsiang CY. (2007) Noninvasive nuclear factor-kappaB bioluminescence imaging for the assessment of host-biomaterial interaction in transgenic mice. Biomaterials. 28(30):4370-7.

Izmailova ES, Paz N, Alencar H, Chun M, Schopf L, Hepperle M, Lane JH, Harriman G, Xu Y, Ocain T, Weissleder R, Mahmood U, Healy AM, Jaffee B. (2007) Use of molecular imaging to quantify response to IKK-2 inhibitor treatment in murine arthritis. Arthritis Rheum. 56(1):117-28.

Partridge J, Carlsen H, Enesa K, Chaudhury H, Zakkar M, Luong L, Kinderlerer A, Johns M, Blomhoff R, Mason JC, Haskard DO, Evans PC. (2007) Laminar shear stress acts as a switch to regulate divergent functions of NF-kappaB in endothelial cells. FASEB J. 21(13):3553-61.

Dohlen G, Odland HH, Carlsen H, Blomhoff R, Thaulow E, Saugstad OD. (2008) Antioxidant activity in the newborn brain: a luciferase mouse model. Neonatology. 93(2):125-31.

Notebaert S, Carlsen H, Janssen D, Vandenabeele P, Blomhoff R, Meyer E. (2008) In vivo imaging of NF-kappaB activity during Escherichia coli-induced mammary gland infection. Cell Microbiol. 10(6):1249-58.

Vykhovanets EV, Shukla S, MacLennan GT, Resnick MI, Carlsen H, Blomhoff R, Gupta S. (2008) Molecular imaging of NF-kappaB in prostate tissue after systemic administration of IL-1 beta. Prostate. 68(1):34-41.

Tukhvatulin AI, Logunov DY, Gitlin II, Shmarov MM, Kudan PV, Adzhieva CA, Moroz AF, Kostyukova NN, Burdelya LG, Naroditsky BS, Gintsburg AL, Gudkov AV. (2011) A In Vitro and In Vivo Study of the Ability of NOD1 Ligands to Activate the Transcriptional Factor NF-κB. Acta Naturae. 3(1):77-84.

Morlacchi S, Dal Secco V, Soldani C, Glaichenhaus N, Viola A, Sarukhan A. (2011) Regulatory T cells target chemokine secretion by dendritic cells independently of their capacity to regulate T cell proliferation. J Immunol. 186(12):6807-14.

Jung K, Lee JE, Kim HZ, Kim HM, Park BS, Hwang SI, Lee JO, Kim SC, Koh GY. (2009) Toll-like receptor 4 decoy, TOY, attenuates gram-negative bacterial sepsis. PLoS One. 4(10):e7403.



Conditions of Use
Title to the LPTA® Models is not transferred to researcher. Researcher has only the following limited rights to use the LPTA® Models. Researcher may obtain derivatives from the LPTA® Models, consisting of tissues or organs, for their research use, however researcher shall have no right to establish luciferase containing cell lines from such derivatives. Researcher may not breed or propagate the LPTA® Models without the prior express written consent of Taconic. Researcher may not transfer the LPTA® Models or any derivatives to a third party. TACONIC MAKES NO REPRESENTATIONS OR WARRANTIES OF ANY KIND, EITHER EXPRESSED OR IMPLIED,INCLUDING FOR NON-INFRINGEMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE WITH REGARDS TO THE LPTA® MODELS.

Use of the LPTA® Models may require a license to perform certain methods of non-invasive in vivo imaging of mammals that are covered by patents controlled by Caliper Life Sciences, Inc., including without limitation U.S. Patent Nos. 5,650,135; 6,217,847; 7,198,774; 6,649,143; 6,939,533; 6,916,462; 6,923,951; 6,890,515; and 6,908,605. The purchase of the LPTA® Models does not convey any license rights under such patents. Researcher should contact Caliper Life Sciences, Inc. to obtain license rights to such patents.

NFκB Activation by LPS
Figure 1. The mice (n=3) were imaged at T= 0 (pretreatment) and 4, 7, and 24 hours following intraperitoneal injection of LPS (1mg/kg) (A). Photons/sec quantified from liver and whole body. The data (B) represent mean fold of induction

NFκB Activation by TNFα
Figure 2. The mice (n=3) were imaged at T=0 (pretreatment) and 4, 7, and 24 hours following intraperitoneal injection of TNFα (2 ìg/mouse) (A). Photons/sec quantified from liver and whole body. The data (B) represent mean fold of induction.

Basal expression
Figure 3. Basal expression. Ubiquitious expression in the whole body, strong signals in the abdominal and thoracic regions. The whole body signal intensity is 3x109 photons/sec.


Imaging Recommendations

Anesthetize mice prior to injection of luciferin and measurement of luciferase transgene expression. Optimal imaging occurs between 10 and 20 minutes following intraperitoneal injection of luciferin.