Phenotypes associated with this allele

• Allele Symbol: Tg(KRT5-Terf2)POBlas
• Allele Name: transgene insertion PO, Maria A Blasco
• Allele ID: MGI:6258222
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
tg1	Tg(KRT5-Terf2)POBlas/0	involves: C57BL/6 * CBA	MGI:6258418

Genotype
MGI:6258418

tg1

• Allelic Composition: Tg(KRT5-Terf2)POBlas/0
• Genetic Background: involves: C57BL/6 * CBA

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

mortality/aging ( J:102653 )

N • mice are born with normal Mendelian distribution, unlike Tg(KRT5-Terf2)PMBlas transgenic males

integument

increased ear pigmentation ( J:102653 )

• less severe than that observed in Tg(KRT5-Terf2)PMBlas transgenic males

increased foot pigmentation ( J:102653 )

• less severe than that observed in Tg(KRT5-Terf2)PMBlas transgenic males

increased tail pigmentation ( J:102653 )

• less severe than that observed in Tg(KRT5-Terf2)PMBlas transgenic males

increased skin pigmentation ( J:102653 )

• mice exhibit hyperpigmentation of light-exposed skin areas (tail, paws and ear) relative to wild-type controls

• skin hyperpigmentation is less severe than that observed in Tg(KRT5-Terf2)PMBlas transgenic males

increased sensitivity to skin irradiation ( J:102653 )

• UVB-irradiated mice show a significant increase in UV-induced pyrimidine (6-4) photoproducts (6-4 PPs) and of cyclobutyl pyrimidine dimers (CPDs) in skin relative to similarly irradiated wild-type controls

skin photosensitivity ( J:102653 )

• light-exposed areas of the skin (tail and ear) show skin dryness, atrophy, hyperpigmentation, hair loss, hyperplastic and dysplastic lesions, and increased incidence of skin tumors with age

increased skin tumor incidence ( J:102653 )

• older mice develop spontaneous tumors in light-exposed areas of the skin, such as the tail

• 18% of mice exhibit spontaneous skin tumors at 6-12 months of age

• at >1 year of age, 23% of mice show keratoacanthomas and squamous cell carcinomas in the tail, with some mice exhibiting multiple tumors

increased keratoacanthoma incidence ( J:102653 )

increased skin squamous cell carcinoma incidence ( J:102653 )

abnormal keratinocyte physiology ( J:102653 )

• in culture, primary skin keratinocytes are less viable than those from wild-type controls

pigmentation

increased ear pigmentation ( J:102653 )

• less severe than that observed in Tg(KRT5-Terf2)PMBlas transgenic males

increased foot pigmentation ( J:102653 )

• less severe than that observed in Tg(KRT5-Terf2)PMBlas transgenic males

increased tail pigmentation ( J:102653 )

• less severe than that observed in Tg(KRT5-Terf2)PMBlas transgenic males

increased skin pigmentation ( J:102653 )

• mice exhibit hyperpigmentation of light-exposed skin areas (tail, paws and ear) relative to wild-type controls

• skin hyperpigmentation is less severe than that observed in Tg(KRT5-Terf2)PMBlas transgenic males

cellular

decreased telomere length ( J:102653 )

• at 4 months of age, mice have markedly shorter telomeres in tail skin than age-matched wild-type controls

• Q-FISH analysis of metaphases from primary keratinocytes revealed shorter telomeres, increased frequencies of signal-free ends (telomeres with no TTAGGG signal), and more end-to-end fusions lacking TTAGGG repeats at the fusion point relative to wild-type cells

increased cellular sensitivity to alkylating agents ( J:102653 )

• in culture, primary keratinocytes are hypersensitive to increasing doses of mitomycin C (MMC), as determined by survival 5 days after MMC treatment

increased cellular sensitivity to ultraviolet irradiation ( J:102653 )

• UVB-irradiated primary keratinocytes exhibit reduced viability relative to similarly irradiated wild-type keratinocytes

abnormal DNA repair ( J:102653 )

• MMC-treated keratinocytes show a 2-fold increase in complex chromosomal aberrations (breaks, fragments, chromatid crosslinks and tri-radials) relative to MMC-treated wild-type controls, suggesting defective repair of DNA crosslinks

chromosomal instability ( J:102653 )

• Q-FISH analysis of metaphases from primary keratinocytes revealed more complex chromosomal aberrations (chromatid crosslinks, chromosomes with multiple telomeres and interstitial telomeres) relative to wild-type cells

• chromosomal instability is further exacerbated with increasing culture passage

induced chromosome breakage ( J:102653 )

• MMC-treated keratinocytes show twice as many complex chromosomal breaks and fragments as MMC-treated wild-type keratinocytes

neoplasm

increased skin tumor incidence ( J:102653 )

• older mice develop spontaneous tumors in light-exposed areas of the skin, such as the tail

• 18% of mice exhibit spontaneous skin tumors at 6-12 months of age

• at >1 year of age, 23% of mice show keratoacanthomas and squamous cell carcinomas in the tail, with some mice exhibiting multiple tumors

increased keratoacanthoma incidence ( J:102653 )

increased skin squamous cell carcinoma incidence ( J:102653 )

increased incidence of tumors by UV-induction ( J:102653 )

• mice develop papillomas and severe skin ulcerations 18 weeks after the start of chronic UVB irradiation treatment, whereas similarly irradiated wild-type cohorts never develop such lesions

• 30 weeks after the start of UVB irradiation treatment, mice develop rapidly growing skin tumors that result in decreased survival, unlike similarly irradiated wild-type controls

• at time of death, chronically irradiated mice show lesions ranging from pretumoral lesions (actinic keratosis, actinic dermatitis, hyperplasia and dysplasia) to different degrees of squamous cell carcinomas (in situ, well differentiated and poorly differentiated) and fibrosarcomas

homeostasis/metabolism

abnormal DNA repair ( J:102653 )

• MMC-treated keratinocytes show a 2-fold increase in complex chromosomal aberrations (breaks, fragments, chromatid crosslinks and tri-radials) relative to MMC-treated wild-type controls, suggesting defective repair of DNA crosslinks

craniofacial

increased ear pigmentation ( J:102653 )

• less severe than that observed in Tg(KRT5-Terf2)PMBlas transgenic males

growth/size/body

increased ear pigmentation ( J:102653 )

• less severe than that observed in Tg(KRT5-Terf2)PMBlas transgenic males

hearing/vestibular/ear

increased ear pigmentation ( J:102653 )

• less severe than that observed in Tg(KRT5-Terf2)PMBlas transgenic males

limbs/digits/tail

increased tail pigmentation ( J:102653 )

• less severe than that observed in Tg(KRT5-Terf2)PMBlas transgenic males

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
xeroderma pigmentosum		DOID:0050427		J:102653