B6;129-Xpc^tm1Ecf/J

Stock number: 010563
Research areas: Cancer Research

Description

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.

Detailed 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.

Allele

Symbol: Xpc^tm1Ecf
Name: targeted mutation 1, Errol C Friedberg
MGI accession ID: MGI:1859840
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Xpc
Marker name: xeroderma pigmentosum, complementation group C
Chromosome: 6
Strain of origin: 129/Sv
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.