IMPC phenotypes (gene matching)
B6;129-Xpatm1Hvs Trp53tm1Holl Tg(pUR288)1Vij/H
| Status | Available to order |
| EMMA ID | EM:08137 |
| Citation information | RRID:IMSR_EM:08137 Research Resource Identifiers (RRID) are persistent unique ID numbers assigned to help researchers cite key resources (e.g. antibodies, model organisms and software projects) in the biomedical literature to improve transparency and reproducibility in research. See https://www.rrids.org/ for more information. |
| International strain name | B6;129-Xpatm1Hvs Trp53tm1Holl Tg(pUR288)1Vij/H |
| Alternative name | Hupki/XPA/lacZ (B6;129-Trp53tm1holl-Xpatm1Hvs-Tg(pUR288)1Vij) |
| Strain type | Targeted Mutant Strains : Knock-in |
| Allele/Transgene symbol | Trp53tm1Holl, Xpatm1Hvs, Tg(pUR288)1Vij |
| Gene/Transgene symbol | Trp53, Xpa, Tg(pUR288)1Vij |
Information from provider
| Provider | Volker Arlt |
| Provider affiliation | Analytical and Environmental Sciences, King's College London |
| Genetic information | Trp53tm1Holl (Trp53 allele): Exons 4-9 of the endogenous murine Trp53 sequence, which encode the DNA binding domain of the tumour suppressor protein, have been replaced with the homologous human sequence. This human TRP53 knock-in allele is abbreviated as Hupki. Xpatm1Hvs (Xpa allele): In the Xpa knockout allele, exon 3, intron 3, and exon 4 are replaced by a neomycin resistance cassette with a PGK2 promoter. Tg(pUR288)1Vij (pUR288 transgene): The chromosomally integrated transgene comprises approximately 20 tandem copies (per haploid genome) of Pst1-linearised pUR288, which contains the pBR322 origin of replication, an ampicillin resistance gene and the lacZ reporter gene. This reporter gene plasmid can be used to determine spontaneous or mutagen-induced mutation frequencies at the lacZ locus in vivo or in vitro. The plasmid is extracted from the genomic DNA and lacZ mutations are identified by selection in E. coli host cells. |
| Phenotypic information | Mice that are homozygous for the targeted Trp53 mutation (i.e. Hupki) are healthy, fertile and do not display any gross abnormalities. The expression and functional activity of the chimeric Trp53 gene in homozygous Hupki mice is normal. Homozygous Hupki mice that are also homozygous for the targeted Xpa knockout mutation (i.e. Xpa-null) are viable and fertile and do not undergo spontaneous tumour development. Xpa is required for nucleotide excision repair (NER), therefore Xpa-Null mice and cells are completely deficient in NER. Hupki:Xpa-Null mice and embryo fibroblasts are highly sensitive to carcinogens that generate DNA damage normally repaired by NER (e.g. bulky DNA adducts) compared with Hupki:Xpa-wild-type controls (unpublished data). |
| Breeding history | Homozygous Hupki+/+ (129/Sv) mice were crossed with heterozygous Xpa+/-;lacZ+ (C57BL/6) mice to generate Hupki+/-;Xpa+/-;lacZ+ (B6;129/Sv) progeny. These progeny were backcrossed to Hupki+/+ stock to generate Hupki+/+;Xpa+/-;lacZ+ (B6;129/Sv) animals. The strain has been maintained (12+ generations) as Hupki+/+;Xpa+/-;lacZ+ (i.e. matings between Xpa+/- mice) in order to generate both Hupki+/+;Xpa-/-;lacZ+ (Xpa-Null) and Hupki+/+;Xpa+/+;lacZ+ (Xpa-wild-type) offspring on a mixed B6;129/Sv background. Note that the lacZ genotyping PCR does not differentiate between +/- and +/+ genotypes, hence the designation lacZ+ (which does not affect mutation analysis at this locus). |
| References |
|
| Homozygous fertile | yes |
| Homozygous viable | yes |
| Homozygous matings required | no |
| Immunocompromised | not known |
Information from EMMA
| Archiving centre | Mary Lyon Centre at MRC Harwell, Oxford, United Kingdom |
Disease and phenotype information
Orphanet associated rare diseases, based on orthologous gene matching
- Xeroderma pigmentosum / Orphanet_910
MGI phenotypes (allele matching)
- cellular phenotype / MGI
- neoplasm / MGI
- increased tumor incidence / MGI
- decreased thymocyte apoptosis / MGI
- decreased cellular sensitivity to ultraviolet irradiation / MGI
- reddish skin / MGI
- scaly skin / MGI
- abnormal epidermal layer morphology / MGI
- skin edema / MGI
- acanthosis / MGI
- increased cellular sensitivity to ultraviolet irradiation / MGI
- small liver / MGI
- corneal opacity / MGI
- anemia / MGI
- impaired hematopoiesis / MGI
- increased incidence of induced tumors / MGI
- pallor / MGI
- fetal growth retardation / MGI
- increased incidence of tumors by UV-induction / MGI
- abnormal cell physiology / MGI
- embryonic lethality during organogenesis, incomplete penetrance / MGI
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
- small liver / MGI
- abnormal testis morphology / MGI
- Leydig cell hyperplasia / MGI
- seminiferous tubule degeneration / MGI
- abnormal spermatogenesis / MGI
- reddish skin / MGI
- scaly skin / MGI
- abnormal epidermal layer morphology / MGI
- decreased body weight / MGI
- corneal opacity / MGI
- anemia / MGI
- impaired hematopoiesis / MGI
- increased circulating follicle stimulating hormone level / MGI
- skin edema / MGI
- abnormal immune system physiology / MGI
- acanthosis / MGI
- reduced male fertility / MGI
- increased papilloma incidence / MGI
- increased tumor incidence / MGI
- increased incidence of induced tumors / MGI
- increased lung adenocarcinoma incidence / MGI
- increased lung adenoma incidence / MGI
- abnormal epididymis morphology / MGI
- increased liver adenoma incidence / MGI
- pallor / MGI
- abnormal lymphocyte physiology / MGI
- fetal growth retardation / MGI
- increased incidence of tumors by chemical induction / MGI
- increased incidence of tumors by UV-induction / MGI
- decreased testis weight / MGI
- abnormal Langerhans cell physiology / MGI
- abnormal cell physiology / MGI
- increased liver tumor incidence / MGI
- increased NK cell number / MGI
- increased cellular sensitivity to ultraviolet irradiation / MGI
- decreased cellular sensitivity to ultraviolet irradiation / MGI
- increased skin squamous cell carcinoma incidence / MGI
- abnormal base-excision repair / MGI
- increased prostaglandin level / MGI
- abnormal NK cell physiology / MGI
- embryonic lethality during organogenesis, incomplete penetrance / MGI
- abnormal seminiferous tubule epithelium morphology / MGI
Literature references
- Knock-in mice with a chimeric human/murine p53 gene develop normally and show wild-type p53 responses to DNA damaging agents: a new biomedical research tool.;Luo J L, Yang Q, Tong W M, Hergenhahn M, Wang Z Q, Hollstein M, ;2001;Oncogene;20;320-8; 11313961
- Increased susceptibility to ultraviolet-B and carcinogens of mice lacking the DNA excision repair gene XPA.;de Vries A, van Oostrom C T, Hofhuis F M, Dortant P M, Berg R J, de Gruijl F R, Wester P W, van Kreijl C F, Capel P J, van Steeg H, Verbeek S J, ;1995;Nature;377;169-73; 7675086
- Induction of DNA adducts and mutations in spleen, liver and lung of XPA-deficient/lacZ transgenic mice after oral treatment with benzo[a]pyrene: correlation with tumour development.;de Vries A, Dollé M E, Broekhof J L, Muller J J, Kroese E D, van Kreijl C F, Capel P J, Vijg J, van Steeg H, ;1997;Carcinogenesis;18;2327-32; 9450477
- TP53 and lacZ mutagenesis induced by 3-nitrobenzanthrone in Xpa-deficient human TP53 knock-in mouse embryo fibroblasts.;Kucab Jill E, Zwart Edwin P, van Steeg Harry, Luijten Mirjam, Schmeiser Heinz H, Phillips David H, Arlt Volker M, ;2016;DNA repair;39;21-33; 26723900
- Characterising Mutational Spectra of Carcinogens in the Tumour Suppressor Gene TP53 Using Human TP53 Knock-in (Hupki) Mouse Embryo Fibroblasts.;Hölzl-Armstrong Lisa, Kucab Jill E, Korenjak Michael, Luijten Mirjam, Phillips David H, Zavadil Jiri, Arlt Volker M, ;2019;Methods and protocols;2;; 31766274