C57Bl/6.Cg-Gt(ROSA)26tm14.1(CAG-tdTomato)HzeTg(EµEBNA1)26Wln/H

Status

Available to order

EMMA IDEM:16047
Citation informationRRID:IMSR_EM:16047 

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International strain nameC57Bl/6.Cg-Gt(ROSA)26tm14.1(CAG-tdTomato)HzeTg(EµEBNA1)26Wln/H
Alternative nameEµEBNA1.26/tdTRed
Strain typeTargeted Mutant Strains
Allele/Transgene symbolGt(ROSA)26Sortm14.1(CAG-tdTomato)Hze, pEµEBNA1
Gene/Transgene symbolGt(ROSA)26Sor, pEµEBNA1

Information from provider

ProviderJoanna Wilson
Provider affiliationMolecular Biosciences, University of Glasgow
Additional ownerProf Hongkui Zeng, Allen Institute for Brain Science, Seattle, Washington, USA.
Genetic informationTransgenic mice harbouring two separate transgenes: 1st : EµEBNA1, line 26 with the transgene insertion on chromosome 5, 2nd: the transgene CAGtdTRed, line 169 with the transgene insertion on chromosome 6 at the ROSA26 locus.
Phenotypic informationHomozygous:
For EµEBNA1: Lymphoma phenotype as noted for the hemizygous mice. Mice are possibly less robust than hemizygous mice. For tdTRed: homozygous not tested.

Heterozygous:
For EµEBNA1: Mice carrying the transgene (males and females) develop neoplastic B cell lymphoma with associated leukaemia. The hallmark of the lymphoma is enlargement of the spleen (which can be substantial), and can be accompanied by enlargement of liver and/or lymph nodes (to varying degrees). Occasionally other organ involvement (such as kidney) is noted. The enlarged organs are replete with neoplastic cells. Penetrance is 100%, with mice showing signs of tumour development, typically between the ages of 4 and 12 months (mean 223 days) in strain C57Bl/6. The incidence is slightly faster in the Balb/C strain (mean 192 days) and slower in the FVB strain (mean 339 days). For tdTRed: Mice carrying the transgene (males and females) have a visibly red phenotype. From an early age the skin appears red, which continues to be visible in hairless regions (eg tail, ear pinnae) in mature mice . Most internal organs also have a red hue. With imaging, the mice fluoresce red at the wave length of tdTRed (excitation peak at 554nm and emission peak at 581nm) as do cells isolated from tissues. Cells can be separated by FACS from mixtures with non-red cells. In older mice (>180 days) some mice appear to show more signs of aging compared to non-transgenic mice of similar age and as such, the transgene may impact general fitness in older mice.
Breeding historyFor EµEBNA1: The line was generated by DNA microinjection into zygotes (B6D/2 F2 zygote background). The mice of this line (denoted 26) were backcrossed to C57Bl/6 for over 70 generations. However, the live line was lost during COVID lockdown in 2020 and rederived from frozen embryos that were derived from a cross between male transgenic mice (C57Bl/6) to either C57Bl/6 or B6D2 F1 females. Since rederivation, the line has again been backcrossed to C57Bl/6 strain at least 6 times (both males and females) (as well as inter-crossed with siblings at some generations), making the predicted C57Bl/6 contribution to the genome, on average at least 99.22%. For tdTRed: The parental strains: B6.Cg-Gt(ROSA)26Sortm1(CAG-tdTomato)Hze/J mice (strain number 007914) were obtained from the Jackson Laboratory (originally generated by Zeng and colleagues, 2010, Nat. Neu. 13,133-140). These mice carry a transgene inserted into the Gt(ROSA)26Sor locus comprising a CAG promoter-driven red-tdTomato fluorescent protein gene, which has a loxP-flanked STOP cassette preventing transcription of the gene. DelCre mice (Tg(CMV-cre)1Cgn) have been described (Schwenk et al (1995), Nucleic Acids Res 23: 5080–5081, PMID 8559668) and are also available from the Jackson Laboratory (strain number 006054). These mice carry an X-linked Cre expressing transgene under the control of the CMV promoter (with ubiquitous expression). These strains of mice were crossed to induce loxP recombination in germ cells, generating the derivative line tdTRed with deleted STOP cassette, which expresses tdTRed in virtually all cells. This new founder has been continued to be backcrossed to C57Bl/6 (and also intercrossed with negative siblings), selecting for the tdTRed transgene, and was selected against the DelCre transgene in the first generation, which the line no longer carries. This line has been crossed to EµEBNA1 line 26 mice (described above) to generate the double transgenics. Note, these lines separately have been approved for archiving and are in the process.
References
  • bcl-xL and RAG genes are induced and the response to IL-2 enhanced in EmuEBNA-1 transgenic mouse lymphocytes.;Tsimbouri Penelope, Drotar Mark E, Coy Joanna L, Wilson Joanna B, ;2002;Oncogene;21;5182-7; 12140768
  • The oncogenic potential of Epstein-Barr virus nuclear antigen 1 in transgenic mice.;Wilson J B, Levine A J, ;1992;Current topics in microbiology and immunology;182;375-84; 1337032
  • Epstein-Barr virus nuclear antigen-1 and Myc cooperate in lymphomagenesis.;Drotar Mark E, Silva Santiago, Barone Enrico, Campbell Donald, Tsimbouri Penelope, Jurvansu Jaana, Bhatia Pardeep, Klein George, Wilson Joanna B, ;2003;International journal of cancer;106;388-95; 12845679
  • Heterologous prime-boost vaccination protects against EBV antigen-expressing lymphomas.;Rühl Julia, Citterio Carmen, Engelmann Christine, Haigh Tracey, Dzionek Andrzej, Dreyer Johannes, Khanna Rajiv, Taylor Graham S, Wilson Joanna B, Leung Carol S, Münz Christian, ;2019;The Journal of clinical investigation;129;2071-2087; 31042161
  • Lymphomas driven by Epstein-Barr virus nuclear antigen-1 (EBNA1) are dependant upon Mdm2.;AlQarni Sana, Al-Sheikh Yazeed, Campbell Donald, Drotar Mark, Hannigan Adele, Boyle Shelagh, Herzyk Pawel, Kossenkov Andrew, Armfield Kate, Jamieson Lauren, Bailo Mariarca, Lieberman Paul M, Tsimbouri Penelope, Wilson Joanna B, ;2018;Oncogene;37;3998-4012; 29691476
  • Expression of Epstein-Barr virus nuclear antigen-1 induces B cell neoplasia in transgenic mice.;Wilson J B, Bell J L, Levine A J, ;1996;The EMBO journal;15;3117-26; 8670812
  • Epstein-Barr virus nuclear antigen-1 renders lymphocytes responsive to IL-2 but not IL-15 for survival.;Tsimbouri Penelope, Al-Sheikh Yazeed, Drotar Mark E, Cushley William, Wilson Joanna B, ;2008;The Journal of general virology;89;2821-2832; 18931080
Homozygous fertilenot known
Homozygous viablenot known
Homozygous matings requiredno
Immunocompromisedno

Information from EMMA

Archiving centreMary Lyon Centre at MRC Harwell, Oxford, United Kingdom

Disease and phenotype information

IMPC phenotypes (gene matching)
MGI phenotypes (gene matching)
  • abnormal ear pigmentation / MGI
  • decreased circulating LDL cholesterol level / MGI
  • decreased hematocrit / MGI
  • increased leukocyte cell number / MGI
  • decreased neutrophil cell number / MGI
  • extramedullary hematopoiesis / MGI
  • abnormal erythropoiesis / MGI
  • abnormal myocardial fiber morphology / MGI
  • abnormal cell death / MGI
  • increased granulocyte number / MGI
  • increased cell proliferation / MGI
  • alopecia / MGI
  • short snout / MGI
  • abnormal digestive system morphology / MGI
  • gastrointestinal hemorrhage / MGI
  • increased rib number / MGI
  • abnormal pulmonary artery morphology / MGI
  • rectal prolapse / MGI
  • abnormal renal/urinary system morphology / MGI
  • abnormal mammary gland development / MGI
  • abnormal spleen morphology / MGI
  • enlarged spleen / MGI
  • enlarged lymph nodes / MGI
  • dystrophic muscle / MGI
  • absent notochord / MGI
  • abnormal retinal photoreceptor morphology / MGI
  • abnormal neuromuscular synapse morphology / MGI
  • pigmentation phenotype / MGI
  • increased body weight / MGI
  • decreased body weight / MGI
  • decreased body size / MGI
  • retinal degeneration / MGI
  • disorganized retinal layers / MGI
  • abnormal optic nerve morphology / MGI
  • decreased anxiety-related response / MGI
  • circling / MGI
  • hypoactivity / MGI
  • impaired coordination / MGI
  • abnormal eating behavior / MGI
  • limb grasping / MGI
  • increased circulating triglyceride level / MGI
  • increased circulating free fatty acid level / MGI
  • increased circulating HDL cholesterol level / MGI
  • hyperglycemia / MGI
  • anemia / MGI
  • abnormal blood vessel morphology / MGI
  • abnormal mesoderm development / MGI
  • abnormal somite development / MGI
  • decreased trophoblast giant cell number / MGI
  • postnatal growth retardation / MGI
  • impaired wound healing / MGI
  • abnormal humoral immune response / MGI
  • arrested B cell differentiation / MGI
  • arrested T cell differentiation / MGI
  • increased inflammatory response / MGI
  • reduced fertility / MGI
  • reduced female fertility / MGI
  • male infertility / MGI
  • decreased litter size / MGI
  • respiratory distress / MGI
  • abnormal pain threshold / MGI
  • increased thermal nociceptive threshold / MGI
  • abnormal coat/hair pigmentation / MGI
  • abnormal glucose homeostasis / MGI
  • increased circulating insulin level / MGI
  • premature death / MGI
  • abnormal tail morphology / MGI
  • abnormal kidney morphology / MGI
  • abnormal neural tube morphology / MGI
  • no abnormal phenotype detected / MGI
  • abnormal seminiferous tubule morphology / MGI
  • small lymph nodes / MGI
  • abnormal spleen white pulp morphology / MGI
  • abnormal bone marrow cell morphology/development / MGI
  • abnormal megakaryocyte progenitor cell morphology / MGI
  • abnormal proerythroblast morphology / MGI
  • abnormal megakaryocyte morphology / MGI
  • increased mean corpuscular volume / MGI
  • decreased mean corpuscular volume / MGI
  • increased mean platelet volume / MGI
  • hepatic steatosis / MGI
  • abnormal epididymis morphology / MGI
  • vestigial tail / MGI
  • reticulocytosis / MGI
  • abnormal keratinocyte differentiation / MGI
  • decreased circulating corticosterone level / MGI
  • asthenozoospermia / MGI
  • oligozoospermia / MGI
  • abnormal renal tubule morphology / MGI
  • decreased circulating insulin level / MGI
  • abnormal chemical nociception / MGI
  • dilated heart left ventricle / MGI
  • decreased vertical activity / MGI
  • abnormal notochord morphology / MGI
  • abnormal ocular fundus morphology / MGI
  • albuminuria / MGI
  • decreased hemoglobin content / MGI
  • decreased erythrocyte cell number / MGI
  • no phenotypic analysis / MGI
  • vertebral transformation / MGI
  • abnormal lumbar vertebrae morphology / MGI
  • abnormal skeletal muscle fiber morphology / MGI
  • absent allantois / MGI
  • hypospadia / MGI
  • anal atresia / MGI
  • increased erythroid progenitor cell number / MGI
  • abnormal embryonic hematopoiesis / MGI
  • kinked neural tube / MGI
  • epididymal inflammation / MGI
  • nervous system phenotype / MGI
  • abnormal nervous system morphology / MGI
  • kidney cysts / MGI
  • pallor / MGI
  • abnormal neural tube closure / MGI
  • abnormal retinal inner nuclear layer morphology / MGI
  • vascular smooth muscle hypoplasia / MGI
  • skeletal muscle necrosis / MGI
  • abnormal defecation / MGI
  • abnormal heart left ventricle morphology / MGI
  • abnormal circulating lipid level / MGI
  • abnormal hormone level / MGI
  • increased lean body mass / MGI
  • abnormal rod electrophysiology / MGI
  • abnormal cone electrophysiology / MGI
  • caudal body truncation / MGI
  • abnormal vitelline vascular remodeling / MGI
  • abnormal sarcomere morphology / MGI
  • increased compact bone thickness / MGI
  • transmission ratio distortion / MGI
  • abnormal basement membrane morphology / MGI
  • short frontal bone / MGI
  • short nasal bone / MGI
  • increased incidence of tumors by chemical induction / MGI
  • caudal vertebral transformation / MGI
  • cervical vertebral transformation / MGI
  • lumbar vertebral transformation / MGI
  • thoracic vertebral transformation / MGI
  • cervical vertebral fusion / MGI
  • absent caudal vertebrae / MGI
  • small sacral vertebrae / MGI
  • abnormal vertebral column morphology / MGI
  • notochord degeneration / MGI
  • truncated notochord / MGI
  • abnormal platelet morphology / MGI
  • decreased susceptibility to experimental autoimmune encephalomyelitis / MGI
  • increased hematopoietic stem cell number / MGI
  • decreased testis weight / MGI
  • increased energy expenditure / MGI
  • decreased adiponectin level / MGI
  • decreased epididymis weight / MGI
  • abnormal epididymis epithelium morphology / MGI
  • skin inflammation / MGI
  • decreased B-1 B cell number / MGI
  • increased neuronal precursor cell number / MGI
  • increased osteoblast cell number / MGI
  • decreased lymphocyte cell number / MGI
  • decreased cardiac muscle contractility / MGI
  • cachexia / MGI
  • increased susceptibility to injury / MGI
  • decreased circulating cholesterol level / MGI
  • abnormal retinal pigment epithelium morphology / MGI
  • abnormal rostral-caudal axis patterning / MGI
  • glomerulosclerosis / MGI
  • increased oxygen consumption / MGI
  • impaired glucose tolerance / MGI
  • spina bifida occulta / MGI
  • decreased triglyceride level / MGI
  • abnormal renal glomerulus morphology / MGI
  • insulin resistance / MGI
  • muscle phenotype / MGI
  • homeostasis/metabolism phenotype / MGI
  • growth/size/body region phenotype / MGI
  • endocrine/exocrine gland phenotype / MGI
  • cardiovascular system phenotype / MGI
  • immune system phenotype / MGI
  • reproductive system phenotype / MGI
  • skeleton phenotype / MGI
  • hematopoietic system phenotype / MGI
  • increased circulating thyroxine level / MGI
  • increased circulating triiodothyronine level / MGI
  • abnormal skeleton morphology / MGI
  • abnormal body temperature / MGI
  • choroidal neovascularization / MGI
  • abnormal eye electrophysiology / MGI
  • decreased circulating glucose level / MGI
  • increased mean corpuscular hemoglobin / MGI
  • decreased mean corpuscular hemoglobin / MGI
  • decreased angiogenesis / MGI
  • increased bone mass / MGI
  • abnormal cell physiology / MGI
  • increased susceptibility to diet-induced obesity / MGI
  • decreased susceptibility to diet-induced obesity / MGI
  • decreased circulating leptin level / MGI
  • increased circulating leptin level / MGI
  • increased mitochondrial fission / MGI
  • increased apoptosis / MGI
  • abnormal tail development / MGI
  • abnormal spermatid morphology / MGI
  • intestine polyps / MGI
  • abnormal paraxial mesoderm morphology / MGI
  • abnormal podocyte slit diaphragm morphology / MGI
  • decreased CD4-positive, alpha beta T cell number / MGI
  • decreased CD8-positive, alpha-beta T cell number / MGI
  • abnormal granulocyte differentiation / MGI
  • abnormal monocyte differentiation / MGI
  • podocyte foot process effacement / MGI
  • increased germinal center B cell number / MGI
  • decreased B-2 B cell number / MGI
  • decreased mature B cell number / MGI
  • increased megakaryocyte cell number / MGI
  • abnormal bone ossification / MGI
  • retinal photoreceptor degeneration / MGI
  • abnormal medium spiny neuron morphology / MGI
  • retinal outer nuclear layer degeneration / MGI
  • increased circulating tumor necrosis factor level / MGI
  • increased circulating interleukin-1 alpha level / MGI
  • increased circulating interleukin-1 beta level / MGI
  • increased interleukin-17 secretion / MGI
  • decreased survivor rate / MGI
  • increased B cell apoptosis / MGI
  • increased liver iron level / MGI
  • increased spleen iron level / MGI
  • increased circulating iron level / MGI
  • lipofuscinosis / MGI
  • abnormal physiological response to xenobiotic / MGI
  • decreased erythroid progenitor cell number / MGI
  • anal stenosis / MGI
  • hairpin sperm flagellum / MGI
  • increased abdominal fat pad weight / MGI
  • increased trophoblast giant cell number / MGI
  • centrally nucleated skeletal muscle fibers / MGI
  • skeletal muscle endomysial fibrosis / MGI
  • abnormal synaptonemal complex / MGI
  • abnormal mammary gland duct morphology / MGI
  • decreased thymocyte apoptosis / MGI
  • enlarged popliteal lymph nodes / MGI
  • decreased birth body size / MGI
  • impaired somite development / MGI
  • increased total body fat amount / MGI
  • abnormal placenta physiology / MGI
  • abnormal retinal blood vessel morphology / MGI
  • decreased mammary gland epithelial cell proliferation / MGI
  • decreased tumor latency / MGI
  • altered tumor pathology / MGI
  • mortality/aging / MGI
  • integument phenotype / MGI
  • increased bone volume / MGI
  • abnormal double-strand DNA break repair / MGI
  • neonatal lethality, complete penetrance / MGI
  • perinatal lethality, incomplete penetrance / MGI
  • prenatal lethality, complete penetrance / MGI
  • embryonic lethality during organogenesis, complete penetrance / MGI
  • preweaning lethality, complete penetrance / MGI
  • prenatal lethality, incomplete penetrance / MGI
  • embryonic lethality during organogenesis, incomplete penetrance / MGI
  • abnormal anterior visceral endoderm cell migration / MGI
  • increased circulating erythropoietin level / MGI
  • renal tubule atrophy / MGI
  • lethality, complete penetrance / MGI
  • increased mitochondria number / MGI
  • rectal atresia / MGI
  • rectourethral fistula / MGI
  • increased hematopoietic stem cell proliferation / MGI
  • increased food intake / MGI
  • impaired mammary gland growth during pregnancy / MGI
  • decreased paraxial mesoderm size / MGI
  • abnormal skeletal muscle regeneration / MGI
  • testis degeneration / MGI
  • preputial gland inflammation / MGI
  • nervous system inclusion bodies / MGI
  • decreased fatty acid beta-oxidation / MGI
  • epididymis hypertrophy / MGI
  • spermatocele / MGI
  • epididymis fibrosis / MGI
  • increased epididymal cell proliferation / MGI
  • increased epididymal epithelium cell proliferation / MGI
  • increased heart iron level / MGI
  • increased intestinal iron level / MGI

Literature references

  • bcl-xL and RAG genes are induced and the response to IL-2 enhanced in EmuEBNA-1 transgenic mouse lymphocytes.;Tsimbouri Penelope, Drotar Mark E, Coy Joanna L, Wilson Joanna B, ;2002;Oncogene;21;5182-7; 12140768
  • The oncogenic potential of Epstein-Barr virus nuclear antigen 1 in transgenic mice.;Wilson J B, Levine A J, ;1992;Current topics in microbiology and immunology;182;375-84; 1337032
  • Epstein-Barr virus nuclear antigen-1 and Myc cooperate in lymphomagenesis.;Drotar Mark E, Silva Santiago, Barone Enrico, Campbell Donald, Tsimbouri Penelope, Jurvansu Jaana, Bhatia Pardeep, Klein George, Wilson Joanna B, ;2003;International journal of cancer;106;388-95; 12845679
  • Heterologous prime-boost vaccination protects against EBV antigen-expressing lymphomas.;Rühl Julia, Citterio Carmen, Engelmann Christine, Haigh Tracey, Dzionek Andrzej, Dreyer Johannes, Khanna Rajiv, Taylor Graham S, Wilson Joanna B, Leung Carol S, Münz Christian, ;2019;The Journal of clinical investigation;129;2071-2087; 31042161
  • Lymphomas driven by Epstein-Barr virus nuclear antigen-1 (EBNA1) are dependant upon Mdm2.;AlQarni Sana, Al-Sheikh Yazeed, Campbell Donald, Drotar Mark, Hannigan Adele, Boyle Shelagh, Herzyk Pawel, Kossenkov Andrew, Armfield Kate, Jamieson Lauren, Bailo Mariarca, Lieberman Paul M, Tsimbouri Penelope, Wilson Joanna B, ;2018;Oncogene;37;3998-4012; 29691476
  • Expression of Epstein-Barr virus nuclear antigen-1 induces B cell neoplasia in transgenic mice.;Wilson J B, Bell J L, Levine A J, ;1996;The EMBO journal;15;3117-26; 8670812
  • Epstein-Barr virus nuclear antigen-1 renders lymphocytes responsive to IL-2 but not IL-15 for survival.;Tsimbouri Penelope, Al-Sheikh Yazeed, Drotar Mark E, Cushley William, Wilson Joanna B, ;2008;The Journal of general virology;89;2821-2832; 18931080

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