Phenotypes associated with this allele

• Allele Symbol: Tg(KRT5-cre/PGR)1Der
• Allele Name: transgene insertion 1, Dennis R Roop
• Allele ID: MGI:2651408
• Summary: 11 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Dicer1^tm1Snj/Dicer1^tm1Snj Trp53^tm1Brn/Trp53^+ Tg(KRT5-cre/PGR)1Der/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6N * FVB/N * ICR	MGI:5618124
cn2	Dicer1^tm1Snj/Dicer1^tm1Snj Trp53^tm1Brn/Trp53^tm1Brn Tg(KRT5-cre/PGR)1Der/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6N * FVB/N * ICR	MGI:5618123
cn3	Trp53^tm1Brn/Trp53^tm1Brn Tg(KRT5-cre/PGR)1Der/0	involves: 129P2/OlaHsd * C57BL/6N * FVB/N * ICR	MGI:5618126
cn4	Dicer1^tm1Snj/Dicer1^tm1Snj Tg(KRT5-cre/PGR)1Der/0	involves: 129S7/SvEvBrd * C57BL/6 * FVB * ICR	MGI:3809306
cn5	Tg(KRT5-cre/PGR)1Der/0 Trp63^tm2Brd/Trp63^tm3.1Brd	involves: 129S7/SvEvBrd * FVB * ICR	MGI:3798054
cn6	Kras^tm4Tyj/Kras^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(KRT5-cre/PGR)1Der/?	involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * FVB * ICR	MGI:3722605
cn7	Kras^tm4Tyj/Kras^+ Trp53^tm1Brn/Trp53^tm3Glo Tg(KRT5-cre/PGR)1Der/?	involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * FVB * ICR	MGI:3722604
cn8	Kras^tm4Tyj/Kras^+ Trp53^tm1Brn/Trp53^+ Tg(KRT5-cre/PGR)1Der/?	involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * FVB * ICR	MGI:3722603
cn9	Kras^tm4Tyj/Kras^+ Trp53^tm3Glo/Trp53^+ Tg(KRT5-cre/PGR)1Der/?	involves: 129/Sv * C57BL/6 * FVB * ICR	MGI:3722602
cn10	Kras^tm4Tyj/Kras^+ Tg(KRT5-cre/PGR)1Der/?	involves: 129/Sv * C57BL/6 * FVB * ICR	MGI:3722600
cn11	Krt14^tm1Der/Krt14^+ Tg(KRT5-cre/PGR)1Der/?	involves: 129X1/SvJ * FVB * ICR	MGI:3812201

Genotype
MGI:5618124

cn1

• Allelic Composition: Dicer1^tm1Snj/Dicer1^tm1Snj; Trp53^tm1Brn/Trp53⁺; Tg(KRT5-cre/PGR)1Der/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6N * FVB/N * ICR

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

mortality/aging

premature death ( J:216813 )

• 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

increased skin tumor incidence ( J:216813 )

• mice that survive beyond 1 year of age develop skin tumors

• less than 1/4 of mice develop more than a single tumor

increased basal cell carcinoma incidence ( J:216813 )

• mice form mostly basal cell carcinomas

neoplasm

increased skin tumor incidence ( J:216813 )

• mice that survive beyond 1 year of age develop skin tumors

• less than 1/4 of mice develop more than a single tumor

increased basal cell carcinoma incidence ( J:216813 )

• mice form mostly basal cell carcinomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
basal cell carcinoma		DOID:2513		J:216813

Genotype
MGI:5618123

cn2

• Allelic Composition: Dicer1^tm1Snj/Dicer1^tm1Snj; Trp53^tm1Brn/Trp53^tm1Brn; Tg(KRT5-cre/PGR)1Der/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6N * FVB/N * ICR

mortality/aging

premature death ( J:216813 )

• mean survival is 9 months

integument

progressive hair loss ( J:216813 )

• loss of fur by the 5th week of age, with mice nearly devoid of fur and whiskers by 12 weeks of age

abnormal hair shaft morphology ( J:216813 )

abnormal hair follicle morphology ( J:216813 )

• 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

abnormal hair cycle ( J:216813 )

• 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

abnormal epidermis stratum basale morphology ( J:216813 )

• pre-malignant basaloid proliferation is seen

hypergranulosis ( J:216813 )

thick epidermis ( J:216813 )

• increase in thickness of the epidermis with a mean thickness of 51.3 um compared to 24 um in controls

increased skin tumor incidence ( J:216813 )

• 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

increased skin squamous cell carcinoma incidence ( J:216813 )

• 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

abnormal skin physiology ( J:216813 )

• 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

neoplasm

increased skin tumor incidence ( J:216813 )

• 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

increased skin squamous cell carcinoma incidence ( J:216813 )

• 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 Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
squamous cell carcinoma		DOID:1749		J:216813

Genotype
MGI:5618126

cn3

• Allelic Composition: Trp53^tm1Brn/Trp53^tm1Brn; Tg(KRT5-cre/PGR)1Der/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6N * FVB/N * ICR

mortality/aging

premature death ( J:216813 )

• mice die by 20 months of age

integument

integument phenotype ( J:216813 )

N • mice exhibit a normal fur coat at they age

increased skin squamous cell carcinoma incidence ( J:216813 )

• 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

neoplasm

increased skin squamous cell carcinoma incidence ( J:216813 )

• 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

Genotype
MGI:3809306

cn4

• Allelic Composition: Dicer1^tm1Snj/Dicer1^tm1Snj; Tg(KRT5-cre/PGR)1Der/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB * ICR

mortality/aging

premature death ( J:216813 )

• 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

alopecia ( J:139257 )

• at 2 to 3 months of age

progressive hair loss ( J:216813 )

• 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

abnormal hair follicle morphology ( J:216813 )

• interfollicular epidermis exhibits an increase in cellularity

• large amount of DNA damage in the basal layer of follicular epithelium and in the interfollicular epidermis

decreased hair follicle number ( J:216813 )

hair follicle degeneration ( J:216813 )

• hair follicles are debris-laden and mis-oriented and enlarged cells and apoptotic figures are seen surrounding the degraded follicle structure

loss of vibrissae ( J:216813 )

• 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

abnormal epidermal layer morphology ( J:139257 , J:216813 )

• 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)

thick epidermis ( J:216813 )

• increase in thickness of the epidermis with a mean thickness of 42 um compared to 24 um in controls

abnormal skin physiology ( J:216813 )

• increase in the numbers of apoptotic cells in the epidermis

• increase in the numbers of mitotic cells in the epidermis, indicating increased proliferation

growth/size/body

cachexia ( J:216813 )

• several mutants exhibit mild cachexia before death

neoplasm

neoplasm ( J:216813 )

N • no tumors are seen upon death

Genotype
MGI:3798054

cn5

• Allelic Composition: Tg(KRT5-cre/PGR)1Der/0; Trp63^tm2Brd/Trp63^tm3.1Brd
• Genetic Background: involves: 129S7/SvEvBrd * FVB * ICR

cellular

early cellular replicative senescence ( J:100483 )

• following treatment with mifepristonein in utero, mice exhibit an increase in cellular senescence

craniofacial

abnormal craniofacial morphology ( J:100483 )

• at E17.5 following treatment with mifepristonein in utero

limbs/digits/tail

abnormal limb morphology ( J:100483 )

• at E17.5 following treatment with mifepristonein in utero

growth/size/body

weight loss ( J:100483 )

• following treatment with mifepristonein at 8 months of age

skeleton

lordokyphosis ( J:100483 )

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

integument

alopecia ( J:100483 )

• following treatment with mifepristonein at 8 months of age, mice exhibit severe alopecia

abnormal skin morphology ( J:100483 )

• at E17.5 following treatment with mifepristonein in utero or at 8 months of age

abnormal epidermal layer morphology ( J:100483 )

• following treatment with mifepristonein utero, mice exhibit stratified epidermal layer and arrested epidermal morphogenesis

Genotype
MGI:3722605

cn6

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(KRT5-cre/PGR)1Der/?
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * FVB * ICR

neoplasm

decreased incidence of tumors by chemical induction ( J:124222 )

• following treatment with RU486 and TPA, mice develop less tumors than in Kras^tm4Tyj Trp53^tm1Brn/Trp53^tm3Glo Tg(KRT5-cre/PGR)1Der mice

increased squamous cell carcinoma incidence ( J:124222 )

• 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

decreased incidence of tumors by chemical induction ( J:124222 )

• following treatment with RU486 and TPA, mice develop less tumors than in Kras^tm4Tyj Trp53^tm1Brn/Trp53^tm3Glo Tg(KRT5-cre/PGR)1Der mice

Genotype
MGI:3722604

cn7

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Trp53^tm1Brn/Trp53^tm3Glo; Tg(KRT5-cre/PGR)1Der/?
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * FVB * ICR

neoplasm

increased incidence of tumors by chemical induction ( J:124222 )

• following treatment with RU486 and TPA, mice develop more tumors than in Kras^tm4Tyj Trp53^tm1Brn/ Trp53^tm1Brn Tg(KRT5-cre/PGR)1Der mice

increased carcinoma incidence ( J:124222 )

• following treatment with RU486 and TPA, conversion to malignant carcinoma is accelerated relative to in Kras^tm4Tyj Trp53^tm1Brn/ Trp53^tm1Brn Tg(KRT5-cre/PGR)1Der mice

increased spindle cell carcinoma incidence ( J:124222 )

• after RU486 and TPA treatment, 60% of tumors that develop are spindle cell carcinomas

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:124222 )

• following treatment with RU486 and TPA, mice develop more tumors than in Kras^tm4Tyj Trp53^tm1Brn/ Trp53^tm1Brn Tg(KRT5-cre/PGR)1Der mice

Genotype
MGI:3722603

cn8

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Trp53^tm1Brn/Trp53⁺; Tg(KRT5-cre/PGR)1Der/?
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * FVB * ICR

neoplasm

increased carcinoma incidence ( J:124222 )

• after RU486 and TPA treatment, 30% of mice develop skin carcinomas compared to 5% of Kras^tm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes

Genotype
MGI:3722602

cn9

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Trp53^tm3Glo/Trp53⁺; Tg(KRT5-cre/PGR)1Der/?
• Genetic Background: involves: 129/Sv * C57BL/6 * FVB * ICR

neoplasm

increased incidence of tumors by chemical induction ( J:124222 )

• after RU486 and TPA treatment, mice develop three-fold more tumors than Kras^tm4Tyj Trp53^tm1Brn heterozygotes and Kras^tm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes

increased metastatic potential ( J:124222 )

• after RU486 and TPA treatment, 60% of mice develop metastasis in the lungs and/or lymph nodes compared to no wild-type mice

abnormal tumor morphology ( J:124222 )

• after RU486 and TPA treatment, 42% of tumors exhibit aneuplody compared to 23% of Kras^tm4Tyj Trp53^tm1Brn heterozygotes and 20% of Kras^tm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes

• after RU486 and TPA treatment, tumors exhibit centrosome amplification in 3% to 5% of tumors cells

increased carcinoma incidence ( J:124222 )

• after RU486 and TPA treatment, carcinoma development is accelerated compared to in Kras^tm4Tyj Trp53^tm1Brn heterozygotes and Kras^tm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes

• after RU486 and TPA treatment, 90% of mice develop skin carcinomas compared to 30% of Kras^tm4Tyj Trp53^tm1Brn heterozygotes and 5% of Kras^tm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes

cellular

abnormal centrosome morphology ( J:124222 )

• after RU486 and TPA treatment, tumors exhibit centrosome amplification in 3% to 5% of tumors cells

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:124222 )

• after RU486 and TPA treatment, mice develop three-fold more tumors than Kras^tm4Tyj Trp53^tm1Brn heterozygotes and Kras^tm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes

Genotype
MGI:3722600

cn10

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Tg(KRT5-cre/PGR)1Der/?
• Genetic Background: involves: 129/Sv * C57BL/6 * FVB * ICR

neoplasm

increased skin papilloma incidence ( J:124222 )

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

integument

increased skin papilloma incidence ( J:124222 )

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

Genotype
MGI:3812201

cn11

• Allelic Composition: Krt14^tm1Der/Krt14⁺; Tg(KRT5-cre/PGR)1Der/?
• Genetic Background: involves: 129X1/SvJ * FVB * ICR

integument

blistering ( J:67320 )

• 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		DO ID	OMIM ID(s)	Ref(s)
epidermolysis bullosa simplex Dowling-Meara type		DOID:0060735	OMIM:131760	J:67320