Phenotypes associated with this allele

• Allele Symbol: E2f1^tm1.1Dgj
• Allele Name: targeted mutation 1.1, David G Johnson
• Allele ID: MGI:5637520
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	E2f1^tm1.1Dgj/E2f1^tm1.1Dgj	FVB.Cg-E2f1^tm1.1Dgj	MGI:5755412
hm2	E2f1^tm1.1Dgj/E2f1^tm1.1Dgj	involves: FVB	MGI:5755402

Genotype
MGI:5755412

hm1

• Allelic Composition: E2f1^tm1.1Dgj/E2f1^tm1.1Dgj
• Genetic Background: FVB.Cg-E2f1^tm1.1Dgj

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

neoplasm

increased incidence of tumors by UV-induction ( J:212453 )

• following exposure to 3,370 J/m² of UVB (3 times/wk for 48 wks), homozygotes exhibit a 95% incidence of skin tumors (squamous cell carcinomas) at the end of the study relative to a 68% incidence for wild-type controls

• after 5 wks of UVB treatment, homozygotes show a >2-fold increase in p53-positive epidermal keratinocytes relative to similarly treated wild-type controls, indicating increased p53 mutations in response to UV radiation

Genotype
MGI:5755402

hm2

• Allelic Composition: E2f1^tm1.1Dgj/E2f1^tm1.1Dgj
• Genetic Background: involves: FVB

cellular

cellular phenotype ( J:212453 )

N • mutant epidermal keratinocytes show normal apoptotic and proliferative responses in response to acute UVB exposure relative to wild-type controls

abnormal base-excision repair ( J:212453 )

• homozygotes show decreased nucleotide excision repair (NER) efficiency in response to UVB-induced DNA damage

• following a single dose of UVB at 1,000 J/m², levels of the 6-4PP (a DNA photoproduct) remaining in UV-treated epidermal DNA is significantly higher than in similarly treated wild-type controls between 3 and 24 hrs post-UVB treatment

• CPD (another DNA photoproduct) is repaired less efficiently than 6-4PP but a significant difference in CPD removal is noted at 6 and 24 hrs post-UVB treatment

abnormal double-strand DNA break repair ( J:212453 )

• in response to UVB radiation, primary keratinocytes from mutant mice show impaired induction of E2F1 protein relative to wild-type controls

• treatment with doxorubicin, which causes double-strand DNA breakage, increases E2F1 protein levels in mutant MEFs to a lesser extent than in wild-type MEFs

• following exposure to UVB, mutant MEFs show impaired recruitment of E2F1 and decreased association of GCN5, acetylated H3K9, and NER factors with damaged DNA

homeostasis/metabolism

abnormal base-excision repair ( J:212453 )

• homozygotes show decreased nucleotide excision repair (NER) efficiency in response to UVB-induced DNA damage

• following a single dose of UVB at 1,000 J/m², levels of the 6-4PP (a DNA photoproduct) remaining in UV-treated epidermal DNA is significantly higher than in similarly treated wild-type controls between 3 and 24 hrs post-UVB treatment

• CPD (another DNA photoproduct) is repaired less efficiently than 6-4PP but a significant difference in CPD removal is noted at 6 and 24 hrs post-UVB treatment

abnormal double-strand DNA break repair ( J:212453 )

• in response to UVB radiation, primary keratinocytes from mutant mice show impaired induction of E2F1 protein relative to wild-type controls

• treatment with doxorubicin, which causes double-strand DNA breakage, increases E2F1 protein levels in mutant MEFs to a lesser extent than in wild-type MEFs

• following exposure to UVB, mutant MEFs show impaired recruitment of E2F1 and decreased association of GCN5, acetylated H3K9, and NER factors with damaged DNA

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:212453 )

N • homozygotes have normal thymocyte homeostasis and show no signs of testicular atrophy or exocrine gland hyperplasia