A genetic mouse model carrying the nonfunctional xeroderma pigmentosum group G gene.
A genetic mouse model with a disrupted XPG allele was generated by insertion of neo cassette sequences into exon 3 of the XPG gene by using embryonic stem (ES) cell techniques. The xpg-deficient mice showed distinct developmental characteristics. Their body was marked smaller than that in wild-type littermates since the postnatal day 6, and this postnatal growth failure became more severe with developmental proceeding. Their life span was very short, all of the mutants died by postnatal day 23 after showing great weakness and emaciation. In addition, the mutant homozygous mice also showed some progressive neurological signs, like the lower level of activity and a progressive ataxia. Further examination indicated there was developmental retardation of the brain in the mutant mice. Their brain weight, and thickness of cerebral cortex and cerebellar cortex were significant different from the controls. These characteristics, like small size brain, brain developmental retardation and progressive neurological dysfunctions in the homozygotes were similar to the typical clinical phenotype of the XPG patients and Cockayne syndrome, we believe that the xpgdeficient mice will be an animal model for studying the function of the XP-G protein in nucleotide-excision repair and mechanisms related to the clinic symptoms of XP-G and Cockayne syndrome in humans.
Sun
Xue-Zhi
XZ
Environmental and Toxicological Sciences Research Group, National Institute of Radiological Sciences, Chiba 263-8555, Japan. sun_s@nirs.go.jp
Harada
Yoshi-Nobu
YN
Zhang
Rui
R
Cui
Chun
C
Takahashi
Sentaro
S
Fukui
Yoshihiro
Y
D000818:Animals; D002531:Cerebellum / Q000002:abnormalities / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004720:Endonucleases; D018390:Gene Targeting; D051379:Mice; D009687:Nuclear Proteins; D013687:Telencephalon / Q000002:abnormalities / Q000378:metabolism; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5
D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5