|Mice that are homozygous for this targeted mutation of Xpc (xeroderma pigmentosum, complementation group C) are more susceptible to skin cancer after UVB radiation exposure and to liver and lung cancer after chemical carcinogen (acetylaminofluorene) exposure. Homozygotes develop lung tumors as early as 6 months of age. By 16-17 months of age all homozygotes have lung tumors. This mutant mouse strain may be useful in studies of nucleotide excision repair, global genome repair, xeroderma pigmentosum, skin, liver and lung cancer.|
Type Mutant Stock; Spontaneous Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Donating Investigator Errol C. Friedberg, Univ. of Texas Southwestern Med. Center
Mice that are homozygous for the targeted mutation are viable, fertile, and normal in size. No gene product (mRNA) is detected by Northern blot analysis using an exon 11-15 probe of MEFs from homozygotes. A truncated transcript is detected when an exon 7-10 probe is used. MEFs from homozygotes are more sensitive to UV radiation cytotoxicity and exhibit impaired DNA repair. Homozygous mice are more susceptible to skin cancer after UVB radiation exposure and to liver and lung cancer after chemical carcinogen (acetylaminofluorene) exposure. Homozygotes develop lung tumors as early as 6 months of age. By 16-17 months of age all homozygotes have lung tumors. Most classified as adenomas, some as adenocarcinomas and all were Non-small Cell Lung Cancers (NSCLCs). A few tumors progress to malignant metatstatic adenocarcinoma. Heterozygotes exhibit an increased predisposition to skin cancer after exposure to UVB radiation when compared to wild-type controls. This mutant mouse strain may be useful in studies of nucleotide excision repair, global genome repair, xeroderma pigmentosum, skin, liver and lung cancer.
A targeting vector containing neo selection cassette was used to disrupt exon 10 and flanking sequence. The construct was electroporated into unspecified 129 derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. Upon arrival at The Jackson Laboratory the mice were crossed with C57BL/6J once to establish the colony.
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View Related Disease (OMIM) TermsRelated Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.View Mammalian Phenotype TermsMammalian Phenotype Terms provided by MGIassigned by genotype
Xpctm1Ecf/Xpctm1Ecfinvolves: 129 * C57BL/6
- increased lung tumor incidence
The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.
Xpctm1Ecf/Xpc+involves: 129 * SKH1
- integument phenotype
- increased sensitivity to skin irradiation
- cellular phenotype
- increased cellular sensitivity to ultraviolet irradiation
- murine embryonic fibroblasts are more sensitive to UV radiation than wild-type cells (MGI Ref ID J:80212)
- oxidative stress
- increased sensitivity to oxidative stress (MGI Ref ID J:70397)
Xpctm1Ecf/Xpctm1Ecfinvolves: 129 * SKH1
- integument phenotype
- abnormal hair follicle morphology
- cyclobutane pyrimidine dimers are observed in hair follicles after treatment with a total UV dose of 1.0 kJ/m2 (MGI Ref ID J:120007)
- epidermal hyperplasia
- basal cells exhibit hypoplasia after a total UV dose of 1.0 kJ/m2 despite the dose being much below the minimal erythema dose (MGI Ref ID J:120007)
- increased sensitivity to skin irradiation
- cyclobutane pyrimidine dimers are observed in cells within the dermis at a reduced level (4.7% compared to 12% in wild-type mice) after treatment with a total UV dose of 1.0 kJ/m2 (MGI Ref ID J:120007)
- pyridine pirimidone photoproducts accumulate in about 1.8% of epidermal basal cells after treatment with a total UV dose of 1.0 kJ/m2 and no increase in photoproducts with increased exposure (MGI Ref ID J:120007)View Research ApplicationsResearch ApplicationsThis mouse can be used to support research in many areas including:
Increased Tumor Incidence
Adenomas: lung, induced
Other Tissues/Organs: lung
Skin Cancers: Induced
|Allele Name||targeted mutation 1, Errol C Friedberg|
|Allele Type||Targeted (Null/Knockout)|
|Mutation Made By||William Singer, Univ. of Texas Southwestern Med. Center|
|Strain of Origin||129/Sv|
|ES Cell Line Strain||129|
|Gene Symbol and Name||Xpc, xeroderma pigmentosum, complementation group C|
|Gene Common Name(s)||RAD4; XP3; XPCC;|
|Molecular Note||A neomycin resistance cassette replaced exon 10 of the Xpc gene, and portions of the flanking introns. The authors predict that homozygous mutant animals would produce a truncated polypeptide with 27 missense amino acids in place of the last 300 C-terminal amino acids. Northern analysis of primary MEF cells from homozygous mutant embryos detected two anomalous transcripts using an exon 7-10 probe, and no transcript using an exon 11-15 probe. [MGI Ref ID J:38645]|
Cheo DL; Ruven HJ; Meira LB; Hammer RE; Burns DK; Tappe NJ; van Zeeland AA ; Mullenders LH ; Friedberg EC. 1997. Characterization of defective nucleotide excision repair in XPC mutant mice. Mutat Res 374(1):1-9. [PubMed: 9067411] [MGI Ref ID J:38645]
Berg RJ; Rebel H; van der Horst GT; van Kranen HJ; Mullenders LH; van Vloten WA; de Gruijl FR. 2000. Impact of global genome repair versus transcription-coupled repair on ultraviolet carcinogenesis in hairless mice. Cancer Res 60(11):2858-63. [PubMed: 10850428] [MGI Ref ID J:62605]
Boonstra A; van Oudenaren A; Baert M; van Steeg H; Leenen PJ; van der Horst GT; Hoeijmakers JH; Savelkoul HF; Garssen J. 2001. Differential ultraviolet-B-induced immunomodulation in XPA, XPC, and CSB DNA repair-deficient mice. J Invest Dermatol 117(1):141-6. [PubMed: 11442761] [MGI Ref ID J:110895]
Cheo DL; Burns DK; Meira LB; Houle JF; Friedberg EC. 1999. Mutational inactivation of the xeroderma pigmentosum group C gene confers predisposition to 2-acetylaminofluorene-induced liver and lung cancer and to spontaneous testicular cancer in Trp53-/- mice. Cancer Res 59(4):771-5. [PubMed: 10029060] [MGI Ref ID J:52823]
Cheo DL; Meira LB; Burns DK; Reis AM; Issac T; Friedberg EC. 2000. Ultraviolet B radiation-induced skin cancer in mice defective in the Xpc, Trp53, and Apex (HAP1) genes: genotype-specific effects on cancer predisposition and pathology of tumors Cancer Res 60(6):1580-4. [PubMed: 10749126] [MGI Ref ID J:61421]
Cheo DL; Meira LB; Hammer RE; Burns DK; Doughty AT; Friedberg EC. 1996. Synergistic interactions between XPC and p53 mutations in double-mutant mice: neural tube abnormalities and accelerated UV radiation-induced skin cancer. Curr Biol 6(12):1691-4. [PubMed: 8994835] [MGI Ref ID J:103622]
Friedberg EC; Bond JP; Burns DK; Cheo DL; Greenblatt MS; Meira LB; Nahari D; Reis AM. 2000. Defective nucleotide excision repair in xpc mutant mice and its association with cancer predisposition. Mutat Res 459(2):99-108. [PubMed: 10725660] [MGI Ref ID J:61133]
Garssen J; van Steeg H; de Gruijl F; de Boer J; van der Horst GT; van Kranen H; van Loveren H; van Dijk M; Fluitman A; Weeda G; Hoeijmakers JH. 2000. Transcription-coupled and global genome repair differentially influence UV-B-induced acute skin effects and systemic immunosuppression. J Immunol 164(12):6199-205. [PubMed: 10843671] [MGI Ref ID J:112137]
Giglia-Mari G; Theil AF; Mari PO; Mourgues S; Nonnekens J; Andrieux LO; de Wit J; Miquel C; Wijgers N; Maas A; Fousteri M; Hoeijmakers JH; Vermeulen W. 2009. Differentiation driven changes in the dynamic organization of Basal transcription initiation. PLoS Biol 7(10):e1000220. [PubMed: 19841728] [MGI Ref ID J:154596]
Griffin C; Waard H; Deans B; Thacker J. 2005. The involvement of key DNA repair pathways in the formation of chromosome rearrangements in embryonic stem cells. DNA Repair (Amst) 4(9):1019-27. [PubMed: 15979950] [MGI Ref ID J:105008]
Hollander MC; Philburn RT; Patterson AD; Velasco-Miguel S; Friedberg EC; Linnoila RI; Fornace AJ Jr. 2005. Deletion of XPC leads to lung tumors in mice and is associated with early events in human lung carcinogenesis. Proc Natl Acad Sci U S A 102(37):13200-5. [PubMed: 16141330] [MGI Ref ID J:101421]
Hoogervorst EM; van Oostrom CT; Beems RB; van Benthem J; van den Berg J; van Kreijl CF; Vos JG; de Vries A; van Steeg H. 2005. 2-AAF-induced tumor development in nucleotide excision repair-deficient mice is associated with a defect in global genome repair but not with transcription coupled repair. DNA Repair (Amst) 4(1):3-9. [PubMed: 15533832] [MGI Ref ID J:94445]
Jaarsma D; van der Pluijm I; de Waard MC; Haasdijk ED; Brandt R; Vermeij M; Rijksen Y; Maas A; van Steeg H; Hoeijmakers JH; van der Horst GT. 2011. Age-related neuronal degeneration: complementary roles of nucleotide excision repair and transcription-coupled repair in preventing neuropathology. PLoS Genet 7(12):e1002405. [PubMed: 22174697] [MGI Ref ID J:179808]
Jansen JG; Tsaalbi-Shtylik A; Hendriks G; Gali H; Hendel A; Johansson F; Erixon K; Livneh Z; Mullenders LH; Haracska L; de Wind N. 2009. Separate domains of Rev1 mediate two modes of DNA damage bypass in mammalian cells. Mol Cell Biol 29(11):3113-23. [PubMed: 19332561] [MGI Ref ID J:149144]
Klein JC; Beems RB; Zwart PE; Hamzink M; Zomer G; Steeg Hv; Kreijl CF. 2001. Intestinal toxicity and carcinogenic potential of the food mutagen 2-amino-1-methyl-6-phenylimidazo. Carcinogenesis 22(4):619-26. [PubMed: 11285198] [MGI Ref ID J:68477]
Kolgen W; van Steeg H; van der Horst GT; Hoeijmakers JH; van Vloten WA; de Gruijl FR; Garssen J. 2003. Association of transcription-coupled repair but not global genome repair with ultraviolet-B-induced Langerhans cell depletion and local immunosuppression. J Invest Dermatol 121(4):751-6. [PubMed: 14632192] [MGI Ref ID J:85982]
Meira LB; Cheo DL; Reis AM; Claij N; Burns DK; Riele H; Friedberg EC. 2002. Mice defective in the mismatch repair gene Msh2 show increased predisposition to UVB radiation-induced skin cancer. DNA Repair (Amst) 1(11):929-34. [PubMed: 12531020] [MGI Ref ID J:79733]
Meira LB; Devaraj S; Kisby GE; Burns DK; Daniel RL; Hammer RE; Grundy S; Jialal I; Friedberg EC. 2001. Heterozygosity for the mouse Apex gene results in phenotypes associated with oxidative stress. Cancer Res 61(14):5552-7. [PubMed: 11454706] [MGI Ref ID J:70397]
Melis JP; Speksnijder EN; Kuiper RV; Salvatori DC; Schaap MM; Maas S; Robinson J; Verhoef A; van Benthem J; Luijten M; van Steeg H. 2013. Detection of genotoxic and non-genotoxic carcinogens in Xpc(-/-)p53(+/-) mice. Toxicol Appl Pharmacol 266(2):289-97. [PubMed: 23153559] [MGI Ref ID J:193203]
Melis JP; Wijnhoven SW; Beems RB; Roodbergen M; van den Berg J; Moon H; Friedberg E; van der Horst GT; Hoeijmakers JH; Vijg J; van Steeg H. 2008. Mouse models for xeroderma pigmentosum group A and group C show divergent cancer phenotypes. Cancer Res 68(5):1347-53. [PubMed: 18316597] [MGI Ref ID J:132760]
Miccoli L; Burr KL; Hickenbotham P; Friedberg EC; Angulo JF; Dubrova YE. 2007. The combined effects of xeroderma pigmentosum C deficiency and mutagens on mutation rates in the mouse germ line. Cancer Res 67(10):4695-9. [PubMed: 17510396] [MGI Ref ID J:121733]
Nahari D; McDaniel LD; Task LB; Daniel RL; Velasco-Miguel S; Friedberg EC. 2004. Mutations in the Trp53 gene of UV-irradiated Xpc mutant mice suggest a novel Xpc-dependent DNA repair process. DNA Repair (Amst) 3(4):379-86. [PubMed: 15010313] [MGI Ref ID J:88558]
Nijhof JG; van Pelt C; Mulder AA; Mitchell DL; Mullenders LH; de Gruijl FR. 2007. Epidermal stem and progenitor cells in murine epidermis accumulate UV damage despite NER proficiency. Carcinogenesis 28(4):792-800. [PubMed: 17127714] [MGI Ref ID J:120007]
Rebel H; Kram N; Westerman A; Banus S; van Kranen HJ; de Gruijl FR. 2005. Relationship between UV-induced mutant p53 patches and skin tumours, analysed by mutation spectra and by induction kinetics in various DNA-repair-deficient mice. Carcinogenesis 26(12):2123-30. [PubMed: 16051635] [MGI Ref ID J:102840]
Reis AM; Cheo DL; Meira LB; Greenblatt MS; Bond JP; Nahari D; Friedberg EC. 2000. Genotype-specific Trp53 mutational analysis in ultraviolet B radiation-induced skin cancers in Xpc and Xpc Trp53 mutant mice Cancer Res 60(6):1571-9. [PubMed: 10749125] [MGI Ref ID J:61422]
Schenten D; Gerlach VL; Guo C; Velasco-Miguel S; Hladik CL; White CL; Friedberg EC; Rajewsky K; Esposito G. 2002. DNA polymerase kappa deficiency does not affect somatic hypermutation in mice. Eur J Immunol 32(11):3152-60. [PubMed: 12555660] [MGI Ref ID J:80212]
Shen HM; Cheo DL; Friedberg E; Storb U. 1997. The inactivation of the XP-C gene does not affect somatic hypermutation or class switch recombination of immunoglobulin genes. Mol Immunol 34(7):527-33. [PubMed: 9364218] [MGI Ref ID J:43793]
Stout GJ; Westdijk D; Calkhoven DM; Pijper O; Backendorf CM; Willemze R; Mullenders LH; de Gruijl FR. 2005. Epidermal transit of replication-arrested, undifferentiated keratinocytes in UV-exposed XPC mice: an alternative to in situ apoptosis. Proc Natl Acad Sci U S A 102(52):18980-5. [PubMed: 16365302] [MGI Ref ID J:104713]
Tsai PS; Nielen M; van der Horst GT; Colenbrander B; Heesterbeek JA; van Vlissingen JM. 2005. The Effect of DNA Repair Defects on Reproductive Performance in Nucleotide Excision Repair (NER) Mouse Models: An Epidemiological Approach. Transgenic Res 14(6):845-57. [PubMed: 16315091] [MGI Ref ID J:103574]
Verhofstad N; Pennings JL; van Oostrom CT; van Benthem J; van Schooten FJ; van Steeg H; Godschalk RW. 2010. Benzo(a)pyrene induces similar gene expression changes in testis of DNA repair proficient and deficient mice. BMC Genomics 11(1):333. [PubMed: 20504355] [MGI Ref ID J:160673]
Wijnhoven SW; Hoogervorst EM; de Waard H; van der Horst GT; van Steeg H. 2007. Tissue specific mutagenic and carcinogenic responses in NER defective mouse models. Mutat Res 614(1-2):77-94. [PubMed: 16769089] [MGI Ref ID J:118078]
Wijnhoven SW; Kool HJ; Mullenders LH; Slater R; van Zeeland AA; Vrieling H. 2001. DMBA-induced toxic and mutagenic responses vary dramatically between NER-deficient Xpa, Xpc and Csb mice. Carcinogenesis 22(7):1099-106. [PubMed: 11408355] [MGI Ref ID J:70351]
van Oosten M; Rebel H; Friedberg EC; van Steeg H; van Der Horst GT; van Kranen HJ; Westerman A; van Zeeland AA; Mullenders LH; de Gruijl FR. 2000. Differential role of transcription-coupled repair in UVB-induced G2 arrest and apoptosis in mouse epidermis Proc Natl Acad Sci U S A 97(21):11268-73. [PubMed: 11005836] [MGI Ref ID J:65265]
van Oosten M; Stout GJ; Backendorf C; Rebel H; de Wind N; Darroudi F; van Kranen HJ; de Gruijl FR; Mullenders LH. 2005. Mismatch repair protein Msh2 contributes to UVB-induced cell cycle arrest in epidermal and cultured mouse keratinocytes. DNA Repair (Amst) 4(1):81-9. [PubMed: 15533840] [MGI Ref ID J:94447]
van der Horst GT; Meira L; Gorgels TG; de Wit J; Velasco-Miguel S; Richardson JA; Kamp Y; Vreeswijk MP; Smit B; Bootsma D; Hoeijmakers JH; Friedberg EC. 2002. UVB radiation-induced cancer predisposition in Cockayne syndrome group A (Csa) mutant mice DNA Repair (Amst) 1:143-57. [PubMed: 12509261] [MGI Ref ID J:74959]
van der Pluijm I; Garinis GA; Brandt RM; Gorgels TG; Wijnhoven SW; Diderich KE; de Wit J; Mitchell JR; van Oostrom C; Beems R; Niedernhofer LJ; Velasco S; Friedberg EC; Tanaka K; van Steeg H; Hoeijmakers JH; van der Horst GT. 2006. Impaired genome maintenance suppresses the growth hormone--insulin-like growth factor 1 axis in mice with Cockayne syndrome. PLoS Biol 5(1):e2. [PubMed: 17326724] [MGI Ref ID J:122013]
Animal Health ReportsProduction of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
Breeding & Husbandry When maintaining a live colony, these mice can be bred as homozygotes. However, homozygotes develop lung tumors as early as 6 months of age. By 16-17 months of age all homozygotes have lung tumors.
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Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2140.00
At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We willfulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of 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 about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
|Pricing for International shipping destinations|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2782.00
Cryorecovery - Standard.
Progeny testing is not required.
|Considerations for Choosing Controls|
|Control Pricing Information for Genetically Engineered Mutant Strains.|
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