C57BL/6-Trp53tm2359Arte/H

Status

Available to order

EMMA IDEM:13118
Citation informationRRID:IMSR_EM:13118 

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International strain nameC57BL/6-Trp53tm2359Arte/H
Alternative name Trp53flR245W-GFP/wt
Strain typeTargeted Mutant Strains : Conditional mutation
Allele/Transgene symbolTrp53tm2359Arte
Gene/Transgene symbolTrp53

Information from provider

ProviderPhilip H Jones
Provider affiliationWellcome Sanger Institute
Genetic informationTrp53flR245W-GFP/wt knock-in mice were generated by TaconicArtemis Gmbh, Germany. In the targeting vector, exons 5 to 11 of the wild-type Trp53 gene were flanked by loxP sites and an additional transcriptional STOP cassette inserted between the Trp53 3’ untranslated region (UTR) and the distal loxP site, in order to prevent transcriptional read-through to downstream exons. A second Trp53 genomic region from exon 5 to exon 11, including the splice acceptor site of intron 4 was introduced 3’ of the distal LoxP site. This duplicated region included a Trp53R245W mutation introduced into exon 7 and a cassette including a glycine-serine-glycine flexible linker, a self-cleaving T2A peptide and the eGFP coding sequences inserted into exon 11, between the last codon of Trp53 and the translation termination codon. Two positive selection markers were also introduced. A neomycin resistance gene flanked by Frt sites was inserted 3’ of the 5’ loxP site in exon 4, downstream of the predicted transcriptional initiation site. A puromycin resistance gene flanked by F3 sites was placed downstream of the 3’ UTR from the duplicated region. The targeting vector was generated using BAC clones from the C57BL/6J RPCIB-731 BAC library and was fully sequenced. After transfection into the C57BL/6NTac embryonic stem cell line, clones that had undergone homologous recombination were selected using puromycin and neomycin and screened by Southern blotting. The conditional Trp53 strain was generated by Flp recombinase-mediated deletion of the selection markers. Prior to cre recombinase-mediated recombination these animals (p53*/wt) express TRP53 protein from two wild-type alleles. Once the wild-type Trp53 genomic region is deleted by cre both the Trp53 mutant carrying the R245W mutation and the eGFP reporter are transcribed.
Phenotypic informationHomozygous:
Homozygous mice have no phenotype as both wild-type alleles of Trp53 are expressed.

Heterozygous:
Heterozygous mice have no phenotype as both wild-type alleles of Trp53 are expressed.
Breeding historyMaintained on C57BL/6 background as heterozygote. May be bred to homozygosity with no phenotype.
References
  • Epidermal Tissue Adapts to Restrain Progenitors Carrying Clonal p53 Mutations.;Murai Kasumi, Skrupskelyte Greta, Piedrafita Gabriel, Hall Michael, Kostiou Vasiliki, Ong Swee Hoe, Nagy Tibor, Cagan Alex, Goulding David, Klein Allon M, Hall Benjamin A, Jones Philip H, ;2018;Cell stem cell;23;687-699.e8; 30269904
  • Outcompeting p53-Mutant Cells in the Normal Esophagus by Redox Manipulation.;Fernandez-Antoran David, Piedrafita Gabriel, Murai Kasumi, Ong Swee Hoe, Herms Albert, Frezza Christian, Jones Philip H, ;2019;Cell stem cell;25;329-341.e6; 31327664
Homozygous fertileyes
Homozygous viableyes
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)
  • increased startle reflex / IMPC
  • increased large unstained cell number / IMPC
  • preweaning lethality, incomplete penetrance / IMPC
  • abnormal retina morphology / IMPC
  • persistence of hyaloid vascular system / IMPC
  • decreased circulating creatine kinase level / IMPC
MGI phenotypes (gene matching)
  • decreased bone mineral density / MGI
  • osteopetrosis / MGI
  • kyphosis / MGI
  • lordosis / MGI
  • decreased hematocrit / MGI
  • decreased leukocyte cell number / MGI
  • decreased neutrophil cell number / MGI
  • extramedullary hematopoiesis / MGI
  • enlarged heart / MGI
  • abnormal cell death / MGI
  • decreased bone marrow cell number / MGI
  • altered response to myocardial infarction / MGI
  • abnormal cell proliferation / MGI
  • increased cell proliferation / MGI
  • decreased cell proliferation / MGI
  • abnormal coat/ hair morphology / MGI
  • sparse hair / MGI
  • delayed hair regrowth / MGI
  • intestinal ulcer / MGI
  • abnormal tibia morphology / MGI
  • abnormal digit pigmentation / MGI
  • increased foot pad pigmentation / MGI
  • kinked tail / MGI
  • enlarged liver / MGI
  • liver hypoplasia / MGI
  • abnormal mammary gland development / MGI
  • abnormal spleen morphology / MGI
  • enlarged spleen / MGI
  • small spleen / MGI
  • spleen hyperplasia / MGI
  • spleen hypoplasia / MGI
  • abnormal Peyer's patch morphology / MGI
  • abnormal thymus morphology / MGI
  • small thymus / MGI
  • abnormal tongue morphology / MGI
  • decreased brain size / MGI
  • cerebellum hypoplasia / MGI
  • abnormal cerebellar foliation / MGI
  • absent cerebellum vermis / MGI
  • abnormal cerebellar Purkinje cell layer / MGI
  • exencephaly / MGI
  • small gonad / MGI
  • small testis / MGI
  • abnormal spermatogenesis / MGI
  • decreased sensitivity to skin irradiation / MGI
  • skin lesions / MGI
  • thin dermal layer / MGI
  • decreased body weight / MGI
  • weight loss / MGI
  • decreased body size / MGI
  • increased metastatic potential / MGI
  • abnormal retina morphology / MGI
  • abnormal optic nerve morphology / MGI
  • absent optic nerve / MGI
  • ataxia / MGI
  • abnormal cardiovascular system physiology / MGI
  • abnormal hematopoietic system physiology / MGI
  • anemia / MGI
  • cardiac hypertrophy / MGI
  • abnormal apoptosis / MGI
  • increased mortality induced by gamma-irradiation / MGI
  • postnatal growth retardation / MGI
  • increased inflammatory response / MGI
  • liver inflammation / MGI
  • lung inflammation / MGI
  • vasculitis / MGI
  • increased mammary adenocarcinoma incidence / MGI
  • hemorrhage / MGI
  • testis hypoplasia / MGI
  • neoplasm / MGI
  • abnormal tumor incidence / MGI
  • increased tumor incidence / MGI
  • increased B cell derived lymphoma incidence / MGI
  • increased T cell derived lymphoma incidence / MGI
  • increased leukemia incidence / MGI
  • increased lung adenocarcinoma incidence / MGI
  • increased sarcoma incidence / MGI
  • increased leiomyosarcoma incidence / MGI
  • increased rhabdomyosarcoma incidence / MGI
  • increased carcinoma incidence / MGI
  • increased lung adenoma incidence / MGI
  • increased skin papilloma incidence / MGI
  • decreased tumor incidence / MGI
  • premature death / MGI
  • abnormal limb morphology / MGI
  • abnormal definitive hematopoiesis / MGI
  • no abnormal phenotype detected / MGI
  • muscular atrophy / MGI
  • abnormal spleen white pulp morphology / MGI
  • abnormal spleen marginal zone morphology / MGI
  • increased intestinal adenoma incidence / MGI
  • abnormal megakaryocyte progenitor cell morphology / MGI
  • abnormal lymphocyte morphology / MGI
  • increased teratoma incidence / MGI
  • hepatic steatosis / MGI
  • opacity of vitreous body / MGI
  • abnormal retinal vasculature morphology / MGI
  • increased heart weight / MGI
  • abnormal ocular fundus morphology / MGI
  • decreased erythrocyte cell number / MGI
  • delayed wound healing / MGI
  • increased hemangioma incidence / MGI
  • decreased mortality induced by ionizing radiation / MGI
  • no phenotypic analysis / MGI
  • liver cirrhosis / MGI
  • abnormal cell cycle / MGI
  • abnormal telomere length / MGI
  • thrombocytopenia / MGI
  • decreased neuron apoptosis / MGI
  • decreased cellular sensitivity to gamma-irradiation / MGI
  • colon polyps / MGI
  • gastric polyps / MGI
  • increased hepatocellular carcinoma incidence / MGI
  • decreased liver weight / MGI
  • renal hypoplasia / MGI
  • decreased tumor growth/size / MGI
  • abnormal tumor morphology / MGI
  • increased hemangiosarcoma incidence / MGI
  • oxidative stress / MGI
  • pallor / MGI
  • oral leukoplakia / MGI
  • abnormal thymus physiology / MGI
  • premature aging / MGI
  • increased osteosarcoma incidence / MGI
  • decreased kidney weight / MGI
  • enhanced cellular glucose import / MGI
  • increased mortality induced by ionizing radiation / MGI
  • abnormal chromosome number / MGI
  • aneuploidy / MGI
  • polyploidy / MGI
  • spontaneous chromosome breakage / MGI
  • abnormal cell cycle checkpoint function / MGI
  • abnormal cerebellar cortex morphology / MGI
  • abnormal spine curvature / MGI
  • increased squamous cell carcinoma incidence / MGI
  • increased cellular sensitivity to ionizing radiation / MGI
  • decreased cellular sensitivity to ionizing radiation / MGI
  • increased testicular teratoma incidence / MGI
  • increased incidence of tumors by chemical induction / MGI
  • increased incidence of tumors by ionizing radiation induction / MGI
  • decreased incidence of tumors by chemical induction / MGI
  • decreased circulating insulin-like growth factor I level / MGI
  • increased hematopoietic stem cell number / MGI
  • decreased hematopoietic stem cell number / MGI
  • decreased skeletal muscle mass / MGI
  • decreased testis weight / MGI
  • decreased spleen weight / MGI
  • decreased neuronal precursor cell number / MGI
  • decreased T cell proliferation / MGI
  • liver hyperplasia / MGI
  • pancytopenia / MGI
  • abnormal posterior eye segment morphology / MGI
  • lethargy / MGI
  • increased brain size / MGI
  • growth/size/body region phenotype / MGI
  • cellular phenotype / MGI
  • immune system phenotype / MGI
  • reproductive system phenotype / MGI
  • darkened coat color / MGI
  • increased angiogenesis / MGI
  • abnormal cell physiology / MGI
  • decreased apoptosis / MGI
  • pulmonary fibrosis / MGI
  • thin cerebellar granule layer / MGI
  • optic nerve degeneration / MGI
  • optic nerve hypoplasia / MGI
  • increased medulloblastoma incidence / MGI
  • abnormal mesenchyme morphology / MGI
  • abnormal common myeloid progenitor cell morphology / MGI
  • decreased T cell apoptosis / MGI
  • increased ovary tumor incidence / MGI
  • delayed cellular replicative senescence / MGI
  • intestine polyps / MGI
  • increased liver tumor incidence / MGI
  • abnormal DNA replication / MGI
  • increased pro-B cell number / MGI
  • abnormal male germ cell apoptosis / MGI
  • increased cellular sensitivity to ultraviolet irradiation / MGI
  • decreased cellular sensitivity to ultraviolet irradiation / MGI
  • decreased spleen red pulp amount / MGI
  • increased circulating tumor necrosis factor level / MGI
  • increased circulating interferon-gamma level / MGI
  • increased circulating interleukin-6 level / MGI
  • increased circulating interleukin-3 level / MGI
  • increased circulating interleukin-5 level / MGI
  • decreased survivor rate / MGI
  • decreased common myeloid progenitor cell number / MGI
  • decreased subcutaneous adipose tissue amount / MGI
  • chromosomal instability / MGI
  • abnormal physiological response to xenobiotic / MGI
  • abnormal enterocyte apoptosis / MGI
  • increased enterocyte apoptosis / MGI
  • increased sensitivity to induced cell death / MGI
  • decreased sensitivity to induced cell death / MGI
  • decreased erythroid progenitor cell number / MGI
  • increased pancreas tumor incidence / MGI
  • abnormal thymocyte apoptosis / MGI
  • increased brain tumor incidence / MGI
  • increased adenocarcinoma incidence / MGI
  • increased follicular lymphoma incidence / MGI
  • increased splenic marginal zone lymphoma incidence / MGI
  • increased histiocytic sarcoma incidence / MGI
  • increased splenocyte proliferation / MGI
  • decreased splenocyte apoptosis / MGI
  • increased thymocyte apoptosis / MGI
  • decreased thymocyte apoptosis / MGI
  • abnormal abdominal lymph node morphology / MGI
  • decreased sensitivity to induced morbidity/mortality / MGI
  • increased sensitivity to xenobiotic induced morbidity/mortality / MGI
  • increased tumor latency / MGI
  • abnormal neuron differentiation / MGI
  • increased reproductive system tumor incidence / MGI
  • increased urinary system tumor incidence / MGI
  • increased skin tumor incidence / MGI
  • increased hamartoma incidence / MGI
  • abnormal tumor latency / MGI
  • decreased tumor latency / MGI
  • increased lipoma incidence / MGI
  • increased hibernoma incidence / MGI
  • increased teratocarcinoma incidence / MGI
  • increased fibrosarcoma incidence / MGI
  • increased spindle cell carcinoma incidence / MGI
  • increased adenoma incidence / MGI
  • abnormal hematopoietic stem cell physiology / MGI
  • mortality/aging / MGI
  • postnatal lethality, complete penetrance / MGI
  • postnatal lethality, incomplete 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
  • lethality throughout fetal growth and development, incomplete penetrance / MGI
  • preweaning lethality, incomplete penetrance / MGI
  • increased tail pigmentation / MGI
  • increased fibroblast proliferation / MGI
  • decreased hematopoietic stem cell proliferation / MGI
  • nail dystrophy / MGI
  • increased lymphoma incidence / MGI
  • abnormal tail tip morphology / MGI
  • decreased fibroblast apoptosis / MGI
  • adipose tissue inflammation / MGI

Literature references

  • Epidermal Tissue Adapts to Restrain Progenitors Carrying Clonal p53 Mutations.;Murai Kasumi, Skrupskelyte Greta, Piedrafita Gabriel, Hall Michael, Kostiou Vasiliki, Ong Swee Hoe, Nagy Tibor, Cagan Alex, Goulding David, Klein Allon M, Hall Benjamin A, Jones Philip H, ;2018;Cell stem cell;23;687-699.e8; 30269904
  • Outcompeting p53-Mutant Cells in the Normal Esophagus by Redox Manipulation.;Fernandez-Antoran David, Piedrafita Gabriel, Murai Kasumi, Ong Swee Hoe, Herms Albert, Frezza Christian, Jones Philip H, ;2019;Cell stem cell;25;329-341.e6; 31327664

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