Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

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

Description
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.

Development
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.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related 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).

Lung Cancer

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Xeroderma Pigmentosum, Complementation Group C; XPC   (XPC)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Xpc^tm1Ecf/Xpc^tm1Ecf

        involves: 129 * C57BL/6

• tumorigenesis
• increased lung tumor incidence
  • lung tumors are seen as early as 6 months of age and by 16-17 months of age, all mutants develop tumors   (MGI Ref ID J:101421)
  • incidence and multiplicity of lung tumors increases with age   (MGI Ref ID J:101421)
• • increased lung adenoma incidence
    • most lung tumors are classified as adenomas, with only a few progressing to malignant carcinomas   (MGI Ref ID J:101421)
  • lung adenocarcinoma
    • a few lung tumors progress to malignant carcinomas   (MGI Ref ID J:101421)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Xpc^tm1Ecf/Xpc⁺

        involves: 129 * SKH1

• integument phenotype
• increased sensitivity to skin irradiation
  • basal cells exhibit reduced levels of cyclobutane pyrimidine dimers (8.7% compared to 12% in wild-type mice) after a total UV dose of 1.0 kJ/m²   (MGI Ref ID J:120007)
  • however, no pyridine pirimidone photoproducts accumulate   (MGI Ref ID J:120007)

Xpc^tm1Ecf/Xpc^tm1Ecf

        involves: 129

• 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)

Xpc^tm1Ecf/Xpc^tm1Ecf

        involves: 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 Applications

Research Applications

This mouse can be used to support research in many areas including:

Cancer Research
Increased Tumor Incidence
      Adenomas
      Adenomas: lung
      Adenomas: lung, induced
      Other Tissues/Organs
      Other Tissues/Organs: lung
      Skin Cancers
      Skin Cancers: Induced
Other
      DNA Repair

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Xpctm1Ecf
Allele Name		targeted mutation 1, Errol C Friedberg
Allele Type		Targeted (knock-out)
Common Name(s)		Xpc-;
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
Chromosome		6
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]

Genotyping

Genotyping Information

Genotyping Protocols

Xpc^tm1Ecf, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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]

Additional References

Xpc^tm1Ecf related

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; Hammer RE; Burns DK; Reis A; Friedberg EC. 1997. Genetic interaction between HAP1/REF-1 and p53 [letter] Nat Genet 17(2):145. [PubMed: 9326930]  [MGI Ref ID J:43195]

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]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

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.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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