All Phenotypes Tg(KRT5-Terf2)PMBlas MGI Mouse

prenatal lethality, incomplete penetrance ( J:102653 )

• males are born at a significantly lower frequency than expected

• however, females (which do not express the transgene) are born with normal Mendelian distribution

premature aging ( J:102653 )

• mice exhibit premature deterioration of the skin

sebaceous gland atrophy ( J:102653 )

• tail skin shows atrophy of the sebaceous glands

focal dorsal hair loss ( J:102653 )

• mice develop alopecia of the dorsal skin that becomes more severe with increasing age

hair follicle degeneration ( J:102653 )

• tail skin shows atrophy of the hair follicles

abnormal skin morphology ( J:102653 )

• light-exposed areas of tail and ear skin show areas of dysplastic lesions

increased ear pigmentation ( J:102653 )

epidermal atrophy ( J:102653 )

• tail skin shows areas of epidermal atrophy

epidermal hyperplasia ( J:102653 )

• ear skin shows dysplastic epidermal hyperplasia with atypical and enlarged nuclei and dermis invasion

dry skin ( J:102653 )

• >78% of mice exhibit skin dryness in areas of dorsal hair loss triggered by exposure to light

skin hyperplasia ( J:102653 )

• light-exposed areas of tail and ear skin show areas of hyperplasia

abnormal epidermal pigmentation ( J:102653 )

• in tail skin, the basal cell layer shows accumulation of melanin deposits

increased foot pigmentation ( J:102653 )

increased tail pigmentation ( J:102653 )

• mice exhibit accumulation of melanin in tail skin

increased skin pigmentation ( J:102653 )

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

• skin hyperpigmentation is much more severe than that observed in Tg(KRT5-Terf2)POBlas or Tg(KRT5-Terf2)PNBlas transgenic mice

• >30% of mice develop hyperpigmentation that becomes more severe with increasing age

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

• incidence of spontaneous skin tumors increases with age, with no tumors detected at 6-12 months of age

• at >1 year of age, 50% of mice show keratoacanthomas and squamous cell carcinomas in the tail, with some mice exhibiting multiple tumors

increased keratoacanthoma incidence ( J:102653 )

• at >1 year of age

increased skin squamous cell carcinoma incidence ( J:102653 )

• at >1 year of age, some mice exhibit multiple squamous cell carcinomas (SCCs) in the tail skin

abnormal keratinocyte physiology ( J:102653 )

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

decreased keratinocyte proliferation ( J:102653 )

• in tail skin, basal layer keratinocytes show a significant decrease in proliferating (Ki67+) cells

increased ear pigmentation ( J:102653 )

abnormal epidermal pigmentation ( J:102653 )

• in tail skin, the basal cell layer shows accumulation of melanin deposits

increased foot pigmentation ( J:102653 )

increased tail pigmentation ( J:102653 )

• mice exhibit accumulation of melanin in tail skin

increased skin pigmentation ( J:102653 )

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

• skin hyperpigmentation is much more severe than that observed in Tg(KRT5-Terf2)POBlas or Tg(KRT5-Terf2)PNBlas transgenic mice

• >30% of mice develop hyperpigmentation that becomes more severe with increasing age

abnormal telomere morphology ( J:102653 )

• in tail skin, basal layer keratinocytes show a significantly higher % of gamma-H2AX-positive nuclei than wild-type cells; 60% of these gamma-H2AX DNA damage foci colocalize with the telomeric protein TERF1, indicating dysfunctional telomeres

decreased telomere length ( J:102653 )

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

• tail skin (normally exposed to light) shows telomere shortening as early as 20 days after birth, whereas dorsal skin (partially protected from light by hair) shows telomere shortening at later time points

• at 60 days after birth, both tail and dorsal skin show clear telomere shortening, although the effect is more severe in the tail

• 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

• adult tail skin keratinocytes show a >50% decrease in the length (loss) of the G-strand overhang relative to wild-type controls

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 significantly reduced viability relative to similarly irradiated wild-type keratinocytes

• however, primary keratinocytes show normal sensitivity to gamma irradiation, with no differences in viability relative to similarly irradiated wild-type controls

decreased keratinocyte proliferation ( J:102653 )

• in tail skin, basal layer keratinocytes show a significant decrease in proliferating (Ki67+) cells

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

increased skin tumor incidence ( J:102653 )

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

• incidence of spontaneous skin tumors increases with age, with no tumors detected at 6-12 months of age

• at >1 year of age, 50% of mice show keratoacanthomas and squamous cell carcinomas in the tail, with some mice exhibiting multiple tumors

increased keratoacanthoma incidence ( J:102653 )

• at >1 year of age

increased skin squamous cell carcinoma incidence ( J:102653 )

• at >1 year of age, some mice exhibit multiple squamous cell carcinomas (SCCs) in the tail skin

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

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

increased ear pigmentation ( J:102653 )

sebaceous gland atrophy ( J:102653 )

• tail skin shows atrophy of the sebaceous glands

increased ear pigmentation ( J:102653 )

increased tail pigmentation ( J:102653 )

• mice exhibit accumulation of melanin in tail skin

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

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

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

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

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

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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