Mouse Genome Informatics
cn1
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53+
Tg(KRT5-cre/PGR)1Der/?

involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * FVB * ICR
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• after RU486 and TPA treatment, 30% of mice develop skin carcinomas compared to 5% of Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes


Mouse Genome Informatics
cn2
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm3Glo
Tg(KRT5-cre/PGR)1Der/?

involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * FVB * ICR
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• following treatment with RU486 and TPA, mice develop more tumors than in Krastm4Tyj Trp53tm1Brn/ Trp53tm1Brn Tg(KRT5-cre/PGR)1Der mice
• following treatment with RU486 and TPA, conversion to malignant carcinoma is accelerated relative to in Krastm4Tyj Trp53tm1Brn/ Trp53tm1Brn Tg(KRT5-cre/PGR)1Der mice
• after RU486 and TPA treatment, 60% of tumors that develop are spindle cell carcinomas

homeostasis/metabolism
• following treatment with RU486 and TPA, mice develop more tumors than in Krastm4Tyj Trp53tm1Brn/ Trp53tm1Brn Tg(KRT5-cre/PGR)1Der mice


Mouse Genome Informatics
cn3
    Krastm4Tyj/Kras+
Trp53tm1Brn/Trp53tm1Brn
Tg(KRT5-cre/PGR)1Der/?

involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * FVB * ICR
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• following treatment with RU486 and TPA, mice develop less tumors than in Krastm4Tyj Trp53tm1Brn/Trp53tm3Glo Tg(KRT5-cre/PGR)1Der mice
• after RU486 and TPA treatment, carcinomas that develop following treatment with RU486 and TPA are squamous cell carcinomas with abundant keratin pearls and an absence of spindle cells

homeostasis/metabolism
• following treatment with RU486 and TPA, mice develop less tumors than in Krastm4Tyj Trp53tm1Brn/Trp53tm3Glo Tg(KRT5-cre/PGR)1Der mice


Mouse Genome Informatics
cn4
    Krastm4Tyj/Kras+
Tg(KRT5-cre/PGR)1Der/?

involves: 129/Sv * C57BL/6 * FVB * ICR
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• 7 to 10 weeks after treatment with RU486 to activate the cre transgene, mice develop epidermal papillomas

integument
• 7 to 10 weeks after treatment with RU486 to activate the cre transgene, mice develop epidermal papillomas


Mouse Genome Informatics
cn5
    Krastm4Tyj/Kras+
Trp53tm3Glo/Trp53+
Tg(KRT5-cre/PGR)1Der/?

involves: 129/Sv * C57BL/6 * FVB * ICR
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• after RU486 and TPA treatment, mice develop three-fold more tumors than Krastm4Tyj Trp53tm1Brn heterozygotes and Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
• after RU486 and TPA treatment, 60% of mice develop metastasis in the lungs and/or lymph nodes compared to no wild-type mice
• after RU486 and TPA treatment, 42% of tumors exhibit aneuplody compared to 23% of Krastm4Tyj Trp53tm1Brn heterozygotes and 20% of Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
• after RU486 and TPA treatment, tumors exhibit centrosome amplification in 3% to 5% of tumors cells
• after RU486 and TPA treatment, carcinoma development is accelerated compared to in Krastm4Tyj Trp53tm1Brn heterozygotes and Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
• after RU486 and TPA treatment, 90% of mice develop skin carcinomas compared to 30% of Krastm4Tyj Trp53tm1Brn heterozygotes and 5% of Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes

homeostasis/metabolism
• after RU486 and TPA treatment, mice develop three-fold more tumors than Krastm4Tyj Trp53tm1Brn heterozygotes and Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes


Mouse Genome Informatics
cn6
    Dicer1tm1Snj/Dicer1tm1Snj
Tg(KRT5-cre/PGR)1Der/0
Trp53tm1Brn/Trp53tm1Brn

involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6N * FVB/N * ICR
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mean survival is 9 months

integument
• loss of fur by the 5th week of age, with mice nearly devoid of fur and whiskers by 12 weeks of age
• dysmorphic hair follicles with dyskertotic cells in the follicular epithelium
• regions of increased cellularity with many mitotic figures are seen in the interfollicular epidermal layer and above the basal layer
• large amount of DNA damage in the basal layer of follicular epithelium and in the interfollicular epidermis
• there is some evidence of attempts to form new follicles
• at a time when control hair follicles are in the telogen phase of the hair cycles, mutants show anagen growth phase hairs with dysmorphic follicles, abnormal hair shafts, and dyskertotic cells in the follicular epithelium
• pre-malignant basaloid proliferation is seen
• increase in thickness of the epidermis with a mean thickness of 51.3 um compared to 24 um in controls
• mice develop highly aggressive and numerous skin tumors starting at 7-8 months of age with all mice showing skin tumors by 12-15 months of age
• 41% of mice form multiple tumors
• mice form moderately or poorly differentiated squamous cell carcinomas and nearly half of mutants develop poorly differentiated carcinomas
• poorly or undifferentiated carcinomas are highly invasive
• the number of apoptotic cells in the epidermis is lower than in single conditional Dicer1 mutants
• increase in the numbers of mitotic cells in the epidermis, indicating increased proliferation

tumorigenesis
• mice develop highly aggressive and numerous skin tumors starting at 7-8 months of age with all mice showing skin tumors by 12-15 months of age
• 41% of mice form multiple tumors
• mice form moderately or poorly differentiated squamous cell carcinomas and nearly half of mutants develop poorly differentiated carcinomas
• poorly or undifferentiated carcinomas are highly invasive


Mouse Genome Informatics
cn7
    Dicer1tm1Snj/Dicer1tm1Snj
Tg(KRT5-cre/PGR)1Der/0
Trp53tm1Brn/Trp53+

involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6N * FVB/N * ICR
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mean survival is 13 months, with none surviving beyond 18 months
• lethality before 1 year is unrelated to cancer as no tumors are seen until after 1 year of age

integument
• mice that survive beyond 1 year of age develop skin tumors
• less than 1/4 of mice develop more than a single tumor
• mice form mostly basal cell carcinomas

tumorigenesis
• mice that survive beyond 1 year of age develop skin tumors
• less than 1/4 of mice develop more than a single tumor
• mice form mostly basal cell carcinomas


Mouse Genome Informatics
cn8
    Tg(KRT5-cre/PGR)1Der/0
Trp53tm1Brn/Trp53tm1Brn

involves: 129P2/OlaHsd * C57BL/6N * FVB/N * ICR
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice die by 20 months of age

integument
N
• mice exhibit a normal fur coat at they age
• mice develop spontaneous carcinomas; half of tumors are well-differentiated squamous cell carcinomas, a few are moderately differentiated and poorly differentiated squamous cell carcinomas
• less than 1/4 of mice develop more than a single tumor

tumorigenesis
• mice develop spontaneous carcinomas; half of tumors are well-differentiated squamous cell carcinomas, a few are moderately differentiated and poorly differentiated squamous cell carcinomas
• less than 1/4 of mice develop more than a single tumor


Mouse Genome Informatics
cn9
    Dicer1tm1Snj/Dicer1tm1Snj
Tg(KRT5-cre/PGR)1Der/0

involves: 129S7/SvEvBrd * C57BL/6 * FVB * ICR
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice die as early as 6 months of age, with a mean survival of 16 months and 80% dying by 20 months of age

integument
• at 2 to 3 months of age
• mice begin to lose their fur and whiskers shortly after the 5th week of age, by 10 weeks of age, mice only retain small patches of fur and are devoid of any fur at 3 months of age
• interfollicular epidermis exhibits an increase in cellularity
• large amount of DNA damage in the basal layer of follicular epithelium and in the interfollicular epidermis
• hair follicles are debris-laden and mis-oriented and enlarged cells and apoptotic figures are seen surrounding the degraded follicle structure
• mice begin to lose their whiskers shortly after the 5th week of age, by 10 weeks of age, mice show only a few misshapen whiskers, and mice are devoid of whiskers at 3 months of age
• at 2 to 3 months of age, mice exhibit a roughening of the epidermis (J:139257)
• cells are larger than in wild-type mice and display a senescence phenotype (J:139257)
• mice exhibit a roughened epidermis at 3 months of age (J:216813)
• interfollicular epidermis exhibits an increase in cellularity (J:216813)
• increase in thickness of the epidermis with a mean thickness of 42 um compared to 24 um in controls
• increase in the numbers of mitotic cells in the epidermis, indicating increased proliferation
• increase in the numbers of apoptotic cells in the epidermis

growth/size/body
• several mutants exhibit mild cachexia before death

tumorigenesis
N
• no tumors are seen upon death


Mouse Genome Informatics
cn10
    Tg(KRT5-cre/PGR)1Der/0
Trp63tm2Brd/Trp63tm3.1Brd

involves: 129S7/SvEvBrd * FVB * ICR
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• following treatment with mifepristonein in utero, mice exhibit an increase in cellular senescence

craniofacial
• at E17.5 following treatment with mifepristonein in utero

limbs/digits/tail
• at E17.5 following treatment with mifepristonein in utero

growth/size/body
• following treatment with mifepristonein at 8 months of age

skeleton
• following treatment with mifepristonein at 8 months of age, mice exhibit lordokyphosis that increases with severity as mouse ages

integument
• following treatment with mifepristonein at 8 months of age, mice exhibit severe alopecia
• at E17.5 following treatment with mifepristonein in utero or at 8 months of age
• following treatment with mifepristonein utero, mice exhibit stratified epidermal layer and arrested epidermal morphogenesis


Mouse Genome Informatics
cn11
    Krt14tm1Der/Krt14+
Tg(KRT5-cre/PGR)1Der/?

involves: 129X1/SvJ * FVB * ICR
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
integument
• after application of a topical antiprogestin, RU486, to the forelimbs and chest of newborn pups so that the cre transgene translocates from the cytoplasm to the nucleus of epidermal cells and becomes active, mice developed blisters filled with fluid on the front legs and paws
• blistering occurs within the basal layer of the epidermis

Mouse Models of Human Disease
OMIM IDRef(s)
Epidermolysis Bullosa Simplex, Dowling-Meara Type 131760 J:67320