Phenotypes associated with this allele

• Allele Symbol: Tg(KRT14-cre/ERT)20Efu
• Allele Name: transgene insertion 20, Elaine Fuchs
• Allele ID: MGI:2446606
• Summary: 24 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Pten^tm1Hwu/Pten^tm1Hwu Tgfbr1^tm1.1Karl/Tgfbr1^tm1.1Karl Tg(KRT14-cre/ERT)20Efu/0	involves: 129 * 129S4/SvJae * C57BL/6 * CD-1 * FVB/N	MGI:5487550
cn2	Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ Rn7sk^tm1.1Mfrye/Rn7sk^tm1.1Mfrye Tg(KRT14-cre/ERT)20Efu/0	involves: 129 * C57BL/6NCrl * CBA * CD-1 * SJL	MGI:7386922
cn3	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Trp53^tm1Brn/Trp53^tm1Brn Tg(KRT14-cre/ERT)20Efu/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * CD-1	MGI:6246565
cn4	Kras^tm4Tyj/Kras^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(KRT14-cre/ERT)20Efu/0	involves: 129P2/OlaHsd * 129S4/SvJae * CD-1	MGI:5298084
cn5	Supv3l1^tm2.1Jkl/Supv3l1^tm2.2Jkl Tg(KRT14-cre/ERT)20Efu/0	involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6 * CD-1 * FVB/N	MGI:3833892
cn6	Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^Gt(CC0690)Wtsi/Mob1b^Gt(CC0690)Wtsi Tg(KRT14-cre/ERT)20Efu/0	involves: 129P2/OlaHsd * C57BL/6 * CD-1	MGI:5473848
cn7	Cebpa^tm1Gonz/Cebpa^tm1Gonz Cebpb^tm1Es/Cebpb^tm1Es Tg(KRT14-cre/ERT)20Efu/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1	MGI:5645076
cn8	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(KRT14-cre/ERT)20Efu/0	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:6246562
cn9	Ctnnb1^tm2Kem/Ctnnb1^tm2Kem Tg(KRT14-cre/ERT)20Efu/0	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:5538318
cn10	Grhl1^tm1Jane/Grhl1^tm1Jane Grhl3^tm1Jane/Grhl3^tm3.1Jane Tg(KRT14-cre/ERT)20Efu/0	involves: 129S1/Sv * C57BL/6 * CD-1	MGI:5896360
cn11	Cebpb^tm1Es/Cebpb^tm1Es Tg(KRT14-cre/ERT)20Efu/0	involves: 129S1/Sv * C57BL/6 * CD-1	MGI:5645046
cn12	Rac1^tm1Djk/Rac1^tm1Djk Tg(KRT14-cre/ERT)20Efu/0	involves: 129S4/SvJae * C57BL/6 * CD-1	MGI:3607402
cn13	Kras^tm4Tyj/Kras^+ Tg(KRT14-cre/ERT)20Efu/0	involves: 129S4/SvJae * C57BL/6 * CD-1 * FVB/N	MGI:5659911
cn14	Kras^tm4Tyj/Kras^+ Tg(CAG-HPV16E6E7,-luc)#Mspi/0 Tg(KRT14-cre/ERT)20Efu/0	involves: 129S4/SvJae * C57BL/6 * CD-1 * FVB/N * FVB/NJ	MGI:5659910
cn15	Gt(ROSA)26Sor^tm1(CARD14*)Ribt/Gt(ROSA)26Sor^+ Malt1^tm1c(EUCOMM)Hmgu/Malt1^tm1c(EUCOMM)Hmgu Tg(KRT14-cre/ERT)20Efu/0	involves: 129S6/SvEvTac * C57BL/6NCrl * CD-1	MGI:6460074
cn16	Gt(ROSA)26Sor^tm1(CARD14*)Ribt/Gt(ROSA)26Sor^+ Tg(KRT14-cre/ERT)20Efu/0	involves: 129S6/SvEvTac * C57BL/6NCrl * CD-1	MGI:6460073
cn17	Gt(ROSA)26Sor^tm1(DTA)Jpmb/Gt(ROSA)26Sor^tm1(DTA)Jpmb Tg(KRT14-cre/ERT)20Efu/?	involves: 129S/SvEv * CD-1	MGI:5289774
cn18	Cebpa^tm1Gonz/Cebpa^tm1Gonz Tg(KRT14-cre/ERT)20Efu/0	involves: 129X1/SvJ * C57BL/6 * CD-1	MGI:5645058
cn19	Cdcp1^tm1.2Moas/Cdcp1^tm1.2Moas Gt(ROSA)26Sor^tm1(Smo/EYFP)Amc/Gt(ROSA)26Sor^+ Tg(KRT14-cre/ERT)20Efu/0	involves: 129X1/SvJ * C57BL/6 * CD-1 * FVB/N * SJL	MGI:5478604
cn20	Ppp6c^tm1Shma/Ppp6c^tm1Shma Tg(KRT14-cre/ERT)20Efu/0	involves: C57BL/6 * CBA * CD-1	MGI:5775156
cn21	Cul4a^tm1.1Pz/Cul4a^tm1.1Pz Tg(KRT14-cre/ERT)20Efu/?	involves: C57BL/6 * CD-1	MGI:3851141
cn22	Lama3^tm1Arte/Lama3^tm1Arte Tg(KRT14-cre/ERT)20Efu/0	involves: C57BL/6 * CD-1	MGI:6277933
cn23	Trpv4^tm1.1Ldtk/Trpv4^tm1.1Ldtk Tg(KRT14-cre/ERT)20Efu/0	involves: C57BL/6 * CD-1 * SJL	MGI:5544607
cn24	Sod2^tm1Smel/Sod2^tm1Smel Tg(KRT14-cre/ERT)20Efu/0	involves: C57BL/6J * CD-1	MGI:5804631

Genotype
MGI:5487550

cn1

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tgfbr1^tm1.1Karl/Tgfbr1^tm1.1Karl; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129 * 129S4/SvJae * C57BL/6 * CD-1 * FVB/N

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

Tgfbr1^tm1.1Karl/Tgfbr1^tm1.1Karl Pten^tm1Hwu/Pten^tm1Hwu Tg(KRT14-cre/ERT)20Efu/0 mice develop anal squamous cell carcinoma

neoplasm

increased squamous cell carcinoma incidence ( J:194652 , J:209026 )

• tamoxifen treated mutants to induce cre-mediated deletion of Tgfbr1 and Pten develop head and neck tumors; papillomas progress to squamous cell carcinoma in the head and neck and oral cavity (J:194652)

• treatment with rapamycin 2 weeks after tamoxifen administration delays initiation and reduces progression of papilloma and onset of squamous cell carcinoma (J:194652)

• rapamycin treatment of mice with already established head and neck squamous cell carcinoma results in regression of those tumors; rapamycin decreases cell proliferation and increases apoptosis in these tumors (J:194652)

• anal neoplasms that develop in tamoxifen treated mice originate from squamous epithelia and not from columnar epithelia, indicating squamous cell carcinoma (J:209026)

• invasion into adjacent muscle tissue is seen in some mice (J:209026)

• anal squamous cell carcinoma shows increased levels of proinflammatory cytokines (J:209026)

• all mice develop head and neck squamous cell carcinomas 16 weeks after tamoxifen induction (J:209026)

• rapamycin treatment 2 weeks after tamoxifen administration decreases cell proliferation, and delays and reduces the progression of anal squamous cell carcinoma (J:209026)

increased papilloma incidence ( J:194652 )

• tamoxifen treated mutants to induce cre-mediated deletion of Tgfbr1 and Pten develop head and neck and oral cavity papillomas that progress to squamous cell carcinoma

increased organ/body region tumor incidence ( J:209026 )

• 33% of mice develop visible anal tumors in 6 weeks after tamoxifen treatment

increased oral papilloma incidence ( J:194652 )

digestive/alimentary system

abnormal anal canal morphology ( J:209026 )

• 4 weeks after oral tamoxifen treatment for 5 consecutive days, hyperplasia is seen in the perianal areas

increased oral papilloma incidence ( J:194652 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
anal canal carcinoma		DOID:6126	OMIM:105580	J:209026
head and neck squamous cell carcinoma		DOID:5520	OMIM:275355	J:194652

Genotype
MGI:7386922

cn2

• Allelic Composition: Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; Rn7sk^tm1.1Mfrye/Rn7sk^tm1.1Mfrye; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129 * C57BL/6NCrl * CBA * CD-1 * SJL

integument

abnormal epidermal layer morphology ( J:331226 )

• reduced cellularity in tamoxifen-treated mice from P4

• however, mice recover one month after the last tamoxifen application

Genotype
MGI:6246565

cn3

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * CD-1

Skin hyperpigmentation in Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(KRT14-cre/ERT)20Efu/0 mice but not in Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Trp53^tm1Brn/Trp53^tm1Brn Tg(KRT14-cre/ERT)20Efu/0 mice

integument

abnormal epidermal layer morphology ( J:253611 )

• after tamoxifen i.p. treatment, the epidermis becomes dysplastic with no melanin deposition

abnormal epidermis stratum basale morphology ( J:253611 )

• at day 28 after tamoxifen i.p. treatment, BrdU+ (proliferating) cells and beta-catenin nuclear staining are increased in the basal layer of the epidermis; however, most of the positive cells are multinucleated clumping cells indicating abnormal mitoses associated with epidermal dysplasia

pigmentation

pigmentation phenotype ( J:253611 )

N • mice do NOT develop skin hyperpigmentation after tamoxifen i.p. treatment

N • melanin is mainly distributed in the dermis and less in the epidermis, similar to control mice

Genotype
MGI:5298084

cn4

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * CD-1

neoplasm

increased skin squamous cell carcinoma incidence ( J:172048 )

• lesions are squamous cell carcinomas (SCCs)characterized by fibroblast-like shaped cells and disruption of basal lamina

• numerous microscopic and small invasive SCCs are observed in the dermis of the back skin in addition to the macroscopic lesions

integument

skin lesions ( J:172048 )

• within 2 months of tamoxifen treatment, animals develop rapidly growing ulcerative skin lesions in the back skin

increased skin squamous cell carcinoma incidence ( J:172048 )

• lesions are squamous cell carcinomas (SCCs)characterized by fibroblast-like shaped cells and disruption of basal lamina

• numerous microscopic and small invasive SCCs are observed in the dermis of the back skin in addition to the macroscopic lesions

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
squamous cell carcinoma		DOID:1749		J:172048

Genotype
MGI:3833892

cn5

• Allelic Composition: Supv3l1^tm2.1Jkl/Supv3l1^tm2.2Jkl; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6 * CD-1 * FVB/N

Skin abnormalities in various conditional Supv3l1 mutants

adipose tissue

adipose tissue phenotype ( J:144991 )

N • unlike in Supv3l1^tm2Jkl/Supv3l1^tm2Jkl floxed Tg(Mx1-cre)1Cgn mice, tamoxifen-treated mice exhibit normal growth, body composition, and weights

cardiovascular system

dilated vasculature ( J:144991 )

• in the ears of tamoxifen-treated mice

integument

integument phenotype ( J:144991 )

N • unlike in Supv3l1^tm2Jkl/Supv3l1^tm2Jkl floxed Tg(Mx1-cre)1Cgn mice, tamoxifen-treated mice exhibit normal hair growth

abnormal dermal layer morphology ( J:144991 )

• the ears of tamoxifen-treated mice exhibit chronic inflammation with marked apoptosis and focal intraepithelial lymphocyte infiltrate unlike in mice heterozygous for the floxed allele

hyperkeratosis ( J:144991 )

• the ears of tamoxifen-treated mice

parakeratosis ( J:144991 )

• the ears of tamoxifen-treated mice

acanthosis ( J:144991 )

• the ears of tamoxifen-treated mice

thick epidermis ( J:144991 )

• the ears of tamoxifen-treated mice

reddish skin ( J:144991 )

• the ears of tamoxifen-treated mice are disfigured and have erythromatous swelling unlike in mice heterozygous for the floxed allele

scaly skin ( J:144991 )

• the ears of tamoxifen-treated mice

Genotype
MGI:5473848

cn6

• Allelic Composition: Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz; Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi}; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1

Skin and hair abnormalities and large paws in tamoxifen treated Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Tg(KRT14-cre/ERT)20Efu/0 Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} mice

mortality/aging

premature death ( J:193981 )

• mice treated with tamoxifen at P28 die within 15 to 55 days of treatment

postnatal lethality, complete penetrance ( J:193981 )

• early tamoxifen-treated results in death within 10 to 30 days of birth due to malnutrition

integument

ruffled hair ( J:193981 )

• in tamoxifen-treated mice

parakeratosis ( J:193981 )

• in tamoxifen-treated mice

abnormal keratinocyte morphology ( J:193981 )

• increased centrosome number in keratinocytes from tamoxifen-treated mice

• keratinocytes from tamoxifen-treated mice exhibit multi-polar spindles unlike cells from control mice

• micronuclei in keratinocytes from tamoxifen-treated mice

epidermal hyperplasia ( J:193981 )

• at P16, tamoxifen-treated mice exhibit multilayered hyperplastic epithelium in the interfollicular epidermis and hair follicles and impaired epidermal regression during catagen unlike control mice

wrinkled skin ( J:193981 )

• wrinkle-bear facial skin in tamoxifen-treated mice

increased epidermal stem cell number ( J:193981 )

• in the interfollicular epidermis of tamoxifen-treated mice

abnormal keratinocyte physiology ( J:193981 )

• impaired contact inhibition in keratinocytes from tamoxifen-treated mice

decreased keratinocyte apoptosis ( J:193981 )

• in tamoxifen-treated mice

increased keratinocyte proliferation ( J:193981 )

• 1.5 times in tamoxifen-treated mice at P13

• keratinocyte hyperplasia in mice treated with tamoxifen at P28

cellular

abnormal cell nucleus morphology ( J:193981 )

• micronuclei in keratinocytes from tamoxifen-treated mice

abnormal mitosis ( J:193981 )

• accelerated mitotic exit in keratinocytes from tamoxifen-treated mice

abnormal mitotic spindle morphology ( J:193981 )

• keratinocytes from tamoxifen-treated mice exhibit multi-polar spindles unlike cells from control mice

decreased keratinocyte apoptosis ( J:193981 )

• in tamoxifen-treated mice

increased keratinocyte proliferation ( J:193981 )

• 1.5 times in tamoxifen-treated mice at P13

• keratinocyte hyperplasia in mice treated with tamoxifen at P28

craniofacial

abnormal mouth morphology ( J:193981 )

• tamoxifen-treated mice exhibit hyperplasia of the oral cavity unlike control mice

abnormal lip morphology ( J:193981 )

• tamoxifen-treated mice exhibit hyperplastic and enlarged lips compared with control mice

behavior/neurological

dysphagia ( J:193981 )

• in tamoxifen-treated mice

growth/size/body

abnormal mouth morphology ( J:193981 )

• tamoxifen-treated mice exhibit hyperplasia of the oral cavity unlike control mice

abnormal lip morphology ( J:193981 )

• tamoxifen-treated mice exhibit hyperplastic and enlarged lips compared with control mice

decreased body size ( J:193981 )

• in tamoxifen-treated mice

hearing/vestibular/ear

abnormal ear morphology ( J:193981 )

• tamoxifen-treated mice exhibit hyperplastic and enlarged ears compared with control mice

limbs/digits/tail

abnormal autopod morphology ( J:193981 )

• tamoxifen-treated mice exhibit hyperplastic and enlarged front paws compared with control mice

digestive/alimentary system

dysphagia ( J:193981 )

• in tamoxifen-treated mice

Genotype
MGI:5645076

cn7

• Allelic Composition: Cebpa^tm1Gonz/Cebpa^tm1Gonz; Cebpb^tm1Es/Cebpb^tm1Es; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1

cellular

abnormal keratinocyte differentiation ( J:158721 )

• 4OHT-treated mutant mice show molecular changes in K5, K14, K1, and K10 that are consistent with a defect in the basal to spinous keratinocyte transition

increased keratinocyte proliferation ( J:158721 )

• 4OHT-treated mutant mice show a significant increase in the numbers of BrdU positive S-phase cells in the IFE and ORS keratinocytes relative to controls

• a 4.7-fold increase is noted in BrdU positive basal S-phase keratinocytes

• a ~27-fold increase is noted in in BrdU positive suprabasal S-phase keratinocytes

endocrine/exocrine glands

abnormal sebaceous gland morphology ( J:158721 )

• in 4OHT-treated mutant mice, sebaceous glands contain abnormal looking sebocytes that appear undifferentiated, show reduced cytoplasmic volume, and lack clear fine vacuolation supportive of lipid accumulation

• affected glands show increased cellular density with more closely apposed nuclei and the cells are morphologically similar to reserve undifferentiated cells

abnormal male preputial gland morphology ( J:158721 )

♂ • 4OHT-treated mutant mice show marked atrophy of preputial gland lobules and reduced numbers of clear finely vacuolated sebocytes

abnormal sebocyte morphology ( J:158721 )

• in 4OHT-treated mutant mice, sebaceous glands contain abnormal looking sebocytes that appear undifferentiated

abnormal sebocyte differentiation ( J:158721 )

• 4OHT-treated mutant mice exhibit loss of morphologically distinct differentiated sebocytes in the sebaceous, Meibomian, and preputial glands

• in 4OHT-treated mutant mice, sebaceous gland lobules associated with hair follicles fail to stain with Oil Red O indicating the absence of sebum and terminally differentiated sebocytes

• sebocyte differentiation is blocked as determined by reduced expression of stearoyl-CoA desaturase and melanocortin 5 receptor, two markers of terminal sebocyte differentiation

abnormal Meibomian gland morphology ( J:158721 )

• 4OHT-treated mutant mice display hyperplasia of the Meibomian ducts

Meibomian gland atrophy ( J:158721 )

• 4OHT-treated mutant mice display atrophic Meibomian glands with greatly reduced lobule size and reduced numbers of differentiated sebocytes with clear vacuolated cytoplasm

abnormal sebaceous lipid secretion ( J:158721 )

• 4OHT-treated mutant mice exhibit lack of sebum production

integument

increased keratinocyte proliferation ( J:158721 )

• 4OHT-treated mutant mice show a significant increase in the numbers of BrdU positive S-phase cells in the IFE and ORS keratinocytes relative to controls

• a 4.7-fold increase is noted in BrdU positive basal S-phase keratinocytes

• a ~27-fold increase is noted in in BrdU positive suprabasal S-phase keratinocytes

abnormal sebaceous gland morphology ( J:158721 )

• in 4OHT-treated mutant mice, sebaceous glands contain abnormal looking sebocytes that appear undifferentiated, show reduced cytoplasmic volume, and lack clear fine vacuolation supportive of lipid accumulation

• affected glands show increased cellular density with more closely apposed nuclei and the cells are morphologically similar to reserve undifferentiated cells

abnormal male preputial gland morphology ( J:158721 )

♂ • 4OHT-treated mutant mice show marked atrophy of preputial gland lobules and reduced numbers of clear finely vacuolated sebocytes

abnormal sebocyte morphology ( J:158721 )

• in 4OHT-treated mutant mice, sebaceous glands contain abnormal looking sebocytes that appear undifferentiated

abnormal sebocyte differentiation ( J:158721 )

• 4OHT-treated mutant mice exhibit loss of morphologically distinct differentiated sebocytes in the sebaceous, Meibomian, and preputial glands

• in 4OHT-treated mutant mice, sebaceous gland lobules associated with hair follicles fail to stain with Oil Red O indicating the absence of sebum and terminally differentiated sebocytes

• sebocyte differentiation is blocked as determined by reduced expression of stearoyl-CoA desaturase and melanocortin 5 receptor, two markers of terminal sebocyte differentiation

abnormal Meibomian gland morphology ( J:158721 )

• 4OHT-treated mutant mice display hyperplasia of the Meibomian ducts

Meibomian gland atrophy ( J:158721 )

• 4OHT-treated mutant mice display atrophic Meibomian glands with greatly reduced lobule size and reduced numbers of differentiated sebocytes with clear vacuolated cytoplasm

abnormal sebaceous lipid secretion ( J:158721 )

• 4OHT-treated mutant mice exhibit lack of sebum production

abnormal hair follicle infundibulum morphology ( J:158721 )

• 4OHT-treated mutant mice display focal and regional areas of moderate to severe hyperplasia of the follicular infundibular epithelium and the infundibular outer root sheath (ORS) keratinocytes

hair follicle outer root sheath hyperplasia ( J:158721 )

• 4OHT-treated mutant mice display hyperplasia of the infundibular outer root sheath (ORS) keratinocytes

abnormal epidermal layer morphology ( J:158721 )

• 4OHT-treated mutant mice show defects in epidermal stratified squamous differentiation

abnormal keratinocyte differentiation ( J:158721 )

• 4OHT-treated mutant mice show molecular changes in K5, K14, K1, and K10 that are consistent with a defect in the basal to spinous keratinocyte transition

abnormal epidermis stratum basale morphology ( J:158721 )

• 4OHT-treated mutant mice display a dysplastic, disorganized basal layer with highly abnormal variations in cell and nucleus size

• a 4.7-fold increase is noted in BrdU positive basal S-phase keratinocytes relative to controls

hyperkeratosis ( J:158721 )

• 4OHT-treated mutant mice display a significantly thickened stratum corneum

parakeratosis ( J:158721 )

• 4OHT-treated mutant mice display low levels of parakeratosis

abnormal epidermis stratum spinosum morphology ( J:158721 )

• 4OHT-treated mutant mice display a dysplastic, disorganized spinous layer with highly abnormal variations in cell and nucleus size

• K10, an early marker of the spinous layer and of the basal to spinous transition is significantly reduced

• K1, another early marker of the spinous layer, is delayed in its expression and instead of being expressed in the layer adjacent to the basal cell layer, K1 is not expressed until ~2-3 layers of cells above the basal layers

abnormal epidermis suprabasal layer morphology ( J:158721 )

• a ~27-fold increase is noted in in BrdU positive suprabasal S-phase keratinocytes relative to controls

epidermal hyperplasia ( J:158721 )

• 4OHT-treated mutant mice display hyperplasia of the interfollicular epidemis (IFE) with a significant increase in the number of nucleated epidermal cell layers; focal areas of hyperplasia are detected as early as 4 days and become more extensive and severe at 8, 12, and 18 days after start of 4OHT treatment

• severe regional epidermal hyperplasia of the haired skin eyelid epidermis is observed

renal/urinary system

abnormal male preputial gland morphology ( J:158721 )

♂ • 4OHT-treated mutant mice show marked atrophy of preputial gland lobules and reduced numbers of clear finely vacuolated sebocytes

reproductive system

abnormal male preputial gland morphology ( J:158721 )

♂ • 4OHT-treated mutant mice show marked atrophy of preputial gland lobules and reduced numbers of clear finely vacuolated sebocytes

vision/eye

abnormal eye morphology ( J:158721 )

• 4OHT-treated mutant mice exhibit dry, swollen, and partially closed eyes

abnormal Meibomian gland morphology ( J:158721 )

• 4OHT-treated mutant mice display hyperplasia of the Meibomian ducts

Meibomian gland atrophy ( J:158721 )

• 4OHT-treated mutant mice display atrophic Meibomian glands with greatly reduced lobule size and reduced numbers of differentiated sebocytes with clear vacuolated cytoplasm

dry eyes ( J:158721 )

Genotype
MGI:6246562

cn8

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(KRT14-cre/ERT)20Efu/0 mice show skin hyperpigmentation of ears, paws, mouth, and trunk after tamoxifen treatment

pigmentation

abnormal epidermal pigmentation ( J:253611 )

• increased melanin content in the ear epidermis at day 28 after topical 4-hydroxytamoxife (4HT) induction

• increased melanin content in the dorsal epidermis at day 28 after tamoxifen i.p. treatment

abnormal epidermal melanocyte morphology ( J:253611 )

• a slow but significant increase of melanocyte numbers is noted in the tail epidermis during the first 14 days after topical 4HT induction, followed by a rapid increase thererafter; however, the number of dermal melanocytes is not significantly altered

• after topical 4HT induction, epidermal melanocytes become progressively larger and more dendritic, indicating melanocytic differentiation

• many dendritic melanocytes containing black melanin pigment are observed around p53+ keratinocytes at day 28 after tamoxifen i.p. treatment

• melanocyte number is increased in the dorsal epidermis at day 28 after tamoxifen i.p. treatment

• treatment of 4HT-induced mice with oral imatinib (a Kit inhibitor) results in decreased melanocyte numbers in the epidermis at day P28 relative to vehicle-treated control mice

• intradermal injection of ACK2 (a Kit-neutralizing antibody) reduces the number of melanocytes in the epidermis at days 7 and 14 after 4HT induction relative to vehicle-treated control mice

increased melanocyte number ( J:253611 )

• a slow but significant increase of melanocyte numbers is noted in the tail epidermis during the first 14 days after topical 4HT induction, followed by a rapid increase thererafter

• melanocyte number is increased in the dorsal epidermis at day 28 after tamoxifen i.p. treatment

• treatment of 4HT-induced mice with oral imatinib (a Kit inhibitor) results in decreased melanocyte numbers in the epidermis at day P28 relative to vehicle-treated control mice

• intradermal injection of ACK2 (a Kit-neutralizing antibody) reduces the number of melanocytes in the epidermis at days 7 and 14 after 4HT induction relative to vehicle-treated control mice

abnormal eumelanosome eumelanin content ( J:253611 )

• amount of eumelanin is significantly increased in the epidermis at day 28 after topical 4HT induction

• treatment of tamoxifen-injected mice with oral imatinib (a Kit inhibitor) results in severe reduction of eumelanin production relative to vehicle-treated control mice at day 28

• amount of pheomelanin remains unchanged during topical 4HT induction

hyperpigmentation ( J:253611 )

• at 1 month after tamoxifen i.p. treatment, mice show skin hyperpigmentation on the ears, paws, tail, mouth, and trunk relative to heterozygous control mice

• skin hyperpigmentation is accompanied by beta-catenin and p53 stabilization, preferential induction of p53 target genes, and p53-dependent up-regulation of Kit ligand

• treatment with ACK2 (a Kit-neutralizing antibody) or imatinib (a Kit inhibitor) abolishes the induction of hyperpigmentation, indicating that it requires the KitL/Kit pathway

increased ear pigmentation ( J:253611 )

• hyperpigmentation of the ears at 1 month after tamoxifen i.p. treatment

• topical treatment with 4HT for 14 days induces skin hyperpigmentation on the ear, esp. at >3 weeks after induction

increased foot pigmentation ( J:253611 )

• hyperpigmentation of the paws at 1 month after tamoxifen i.p. treatment

increased tail pigmentation ( J:253611 )

• hyperpigmentation of the tail at 1 month after tamoxifen i.p. treatment

• topical treatment with 4HT for 14 days induces skin hyperpigmentation on the tail, esp. at >3 weeks after induction

integument

increased ear pigmentation ( J:253611 )

• hyperpigmentation of the ears at 1 month after tamoxifen i.p. treatment

• topical treatment with 4HT for 14 days induces skin hyperpigmentation on the ear, esp. at >3 weeks after induction

abnormal epidermis stratum basale morphology ( J:253611 )

• at day 28 after tamoxifen i.p. treatment, BrdU+ (proliferating) cells and beta-catenin nuclear staining are increased in the basal layer of the epidermis

epidermal hyperplasia ( J:253611 )

• after tamoxifen i.p. treatment, the epidermis becomes hyperplastic with increased melanin deposition

• treatment of tamoxifen-injected mice with oral imatinib (a Kit inhibitor) induces thinning of the epidermis with decreased melanin levels in the epidermis relative to vehicle-treated control mice

thick epidermis ( J:253611 )

• increased epidermal thickness in the ears 28 days after topical 4HT induction

abnormal epidermal pigmentation ( J:253611 )

• increased melanin content in the ear epidermis at day 28 after topical 4-hydroxytamoxife (4HT) induction

• increased melanin content in the dorsal epidermis at day 28 after tamoxifen i.p. treatment

abnormal epidermal melanocyte morphology ( J:253611 )

• a slow but significant increase of melanocyte numbers is noted in the tail epidermis during the first 14 days after topical 4HT induction, followed by a rapid increase thererafter; however, the number of dermal melanocytes is not significantly altered

• after topical 4HT induction, epidermal melanocytes become progressively larger and more dendritic, indicating melanocytic differentiation

• many dendritic melanocytes containing black melanin pigment are observed around p53+ keratinocytes at day 28 after tamoxifen i.p. treatment

• melanocyte number is increased in the dorsal epidermis at day 28 after tamoxifen i.p. treatment

• treatment of 4HT-induced mice with oral imatinib (a Kit inhibitor) results in decreased melanocyte numbers in the epidermis at day P28 relative to vehicle-treated control mice

• intradermal injection of ACK2 (a Kit-neutralizing antibody) reduces the number of melanocytes in the epidermis at days 7 and 14 after 4HT induction relative to vehicle-treated control mice

increased foot pigmentation ( J:253611 )

• hyperpigmentation of the paws at 1 month after tamoxifen i.p. treatment

increased tail pigmentation ( J:253611 )

• hyperpigmentation of the tail at 1 month after tamoxifen i.p. treatment

• topical treatment with 4HT for 14 days induces skin hyperpigmentation on the tail, esp. at >3 weeks after induction

abnormal skin physiology ( J:253611 )

• tamoxifen-injected mice show induction of the DNA-damage response, as shown by increased gamma-H2AX staining in the epidermis

cellular

decreased cellular sensitivity to ultraviolet irradiation ( J:253611 )

• 24 h after exposure to a high, sunburn-inducing dose of UVB, hyperpigmented tails of tamoxifen-treated mice show absence of skin swelling and significantly fewer TUNEL+ apoptotic keratinocytes in the tail skin than similarly-treated control mice, indicating protection from UV (sunburn) damage

increased apoptosis ( J:253611 )

• tamoxifen-injected mice show increased apoptosis in the epidermis, as shown by increased cleaved-caspase 3 expression

neoplasm

neoplasm ( J:253611 )

N • no skin tumor formation is observed for at least 9 months after tamoxifen i.p. treatment

growth/size/body

increased ear pigmentation ( J:253611 )

• hyperpigmentation of the ears at 1 month after tamoxifen i.p. treatment

• topical treatment with 4HT for 14 days induces skin hyperpigmentation on the ear, esp. at >3 weeks after induction

craniofacial

increased ear pigmentation ( J:253611 )

• hyperpigmentation of the ears at 1 month after tamoxifen i.p. treatment

• topical treatment with 4HT for 14 days induces skin hyperpigmentation on the ear, esp. at >3 weeks after induction

hearing/vestibular/ear

increased ear pigmentation ( J:253611 )

• hyperpigmentation of the ears at 1 month after tamoxifen i.p. treatment

• topical treatment with 4HT for 14 days induces skin hyperpigmentation on the ear, esp. at >3 weeks after induction

limbs/digits/tail

increased tail pigmentation ( J:253611 )

• hyperpigmentation of the tail at 1 month after tamoxifen i.p. treatment

• topical treatment with 4HT for 14 days induces skin hyperpigmentation on the tail, esp. at >3 weeks after induction

Genotype
MGI:5538318

cn9

• Allelic Composition: Ctnnb1^tm2Kem/Ctnnb1^tm2Kem; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

integument

integument phenotype ( J:204142 )

N • after induction, mutants do not display overt blistering

abnormal epidermal layer morphology ( J:204142 )

• with topical tamoxifen treatment during the first telogen phase, epidermis exhibits increased proliferation as well as expanded expression of basal and suprabasal markers and hyperproliferation markers

immune system

cutaneous mastocytosis ( J:204142 )

• with doxycycline induction from P4-P60, mast cell number in the dermis is increased at P60

hematopoietic system

cutaneous mastocytosis ( J:204142 )

• with doxycycline induction from P4-P60, mast cell number in the dermis is increased at P60

Genotype
MGI:5896360

cn10

• Allelic Composition: Grhl1^tm1Jane/Grhl1^tm1Jane; Grhl3^tm1Jane/Grhl3^tm3.1Jane; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CD-1

mortality/aging

postnatal lethality, complete penetrance ( J:233531 )

• all die within 7 weeks of tamoxifen treatment

integument

impaired skin barrier function ( J:233531 )

• regression of skin barrier function after tamoxifen treatment

• dye penetration is variegated matching the pattern of cre mediated gene deletion

abnormal corneocyte envelope morphology ( J:233531 )

• after tamoxifen treatment gross abnormalities and increased fragility are seen

thick epidermis ( J:233531 )

• after tamoxifen treatment

homeostasis/metabolism

impaired skin barrier function ( J:233531 )

• regression of skin barrier function after tamoxifen treatment

• dye penetration is variegated matching the pattern of cre mediated gene deletion

Genotype
MGI:5645046

cn11

• Allelic Composition: Cebpb^tm1Es/Cebpb^tm1Es; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CD-1

cellular

abnormal keratinocyte differentiation ( J:158721 )

• 4OHT-treated mutant mice show a modest decrease in staining intensity for keratin 10 (K10)

• however, spatial expression patterns for K5, K10, loricrin and involucrin are similar to those in controls

increased keratinocyte proliferation ( J:158721 )

• 4OHT-treated mutant mice show a significant increase in the number of BrdU positive basal keratinocytes following a 1 hour pulse relative to controls

integument

integument phenotype ( J:158721 )

N • 4OHT-treated mutant mice show no major changes in the morphology of interfollicular epidemis, outer root sheath of the hair follicle, and sebaceous glands relative to controls

abnormal keratinocyte differentiation ( J:158721 )

• 4OHT-treated mutant mice show a modest decrease in staining intensity for keratin 10 (K10)

• however, spatial expression patterns for K5, K10, loricrin and involucrin are similar to those in controls

increased keratinocyte proliferation ( J:158721 )

• 4OHT-treated mutant mice show a significant increase in the number of BrdU positive basal keratinocytes following a 1 hour pulse relative to controls

epidermal hyperplasia ( J:158721 )

• 4OHT-treated mutant mice show a significant increase in the number of nucleated cell layers relative to controls

thick epidermis ( J:158721 )

• 4OHT-treated mutant mice show a moderate increase in epidermal thickness relative to controls

Genotype
MGI:3607402

cn12

• Allelic Composition: Rac1^tm1Djk/Rac1^tm1Djk; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CD-1

endocrine/exocrine glands

abnormal sebocyte number ( J:99995 )

• an early increase in the number of terminally differentiated sebocytes is followed by progressive sebocyte loss

enlarged sebaceous gland ( J:99995 )

• 7 to 9 days after tamoxifen treatment sebaceous glands are enlarged and disorganized

integument

abnormal sebocyte number ( J:99995 )

• an early increase in the number of terminally differentiated sebocytes is followed by progressive sebocyte loss

enlarged sebaceous gland ( J:99995 )

• 7 to 9 days after tamoxifen treatment sebaceous glands are enlarged and disorganized

abnormal hair follicle morphology ( J:99995 )

• 11 to 15 days after tamoxifen treatment the hair follicle is reduced in size

absent hair follicle bulb ( J:99995 )

• the hair bulb is reduced and then absent following tamoxifen treatment

abnormal hair follicle infundibulum morphology ( J:99995 )

• 11 to 15 days after tamoxifen treatment the infundibulum degenerates into cysts

abnormal hair follicle bulge morphology ( J:99995 )

• depletion of stem cells is detected by the decreased expression of 3 hair follicle bulge markers

abnormal hair cycle ( J:99995 )

• pronounced defects in hair cycle are seen

abnormal epidermal layer morphology ( J:99995 )

• 3 to 5 days after tamoxifen treatment the interfollicular epidermis is thickened with an increase in cell numbers in the living and cornified layers and the infundibulum at the junction of the interfollicular epidermis and hair follicle is expanded

• 3 to 5 days after tamoxifen treatment the size of hemidesmosomes is reduced and later the numbers are reduced and those remaining are rudimentary

• 11 to 15 days after tamoxifen treatment partial to complete loss of viable interfollicular epidermal cell layers is seen

abnormal epidermis stratum basale morphology ( J:99995 )

• 7 to 9 days after tamoxifen treatment the basal layer is disorganized and has fewer, larger cells

abnormal skin cell number ( J:99995 )

• 3 to 5 days after tamoxifen treatment increased proliferation is seen in the epidermis, however from day 7 on proliferation is reduced

abnormal keratinocyte physiology ( J:99995 )

• in culture, treatment of keratinocytes with tamoxifen blocks clonal growth

Genotype
MGI:5659911

cn13

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CD-1 * FVB/N

neoplasm

increased mouth tumor incidence ( J:210533 )

• tamoxifen treated mice develop oral tumors

digestive/alimentary system

increased mouth tumor incidence ( J:210533 )

• tamoxifen treated mice develop oral tumors

Genotype
MGI:5659910

cn14

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Tg(CAG-HPV16E6E7,-luc)#Mspi/0; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CD-1 * FVB/N * FVB/NJ

neoplasm

increased oral papilloma incidence ( J:210533 )

• tamoxifen treated mice develop oral tumors; tumors grow faster than in single conditional Kras mutants

• oral tumors of tamoxifen treated mice are papillomas that express HPV-biomarkers p16 and MCM7

• 14 days after tamoxifen treatment, mice treated with rapamycin for 3 days exhibit a transient decrease in tumor growth with regrowth after rapamycin is removed

• 14 days after tamoxifen treatment, mice that are treated with image-guided radiotherapy show regression of tumors

digestive/alimentary system

increased oral papilloma incidence ( J:210533 )

• tamoxifen treated mice develop oral tumors; tumors grow faster than in single conditional Kras mutants

• oral tumors of tamoxifen treated mice are papillomas that express HPV-biomarkers p16 and MCM7

• 14 days after tamoxifen treatment, mice treated with rapamycin for 3 days exhibit a transient decrease in tumor growth with regrowth after rapamycin is removed

• 14 days after tamoxifen treatment, mice that are treated with image-guided radiotherapy show regression of tumors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
oral cavity cancer		DOID:8618		J:210533

Genotype
MGI:6460074

cn15

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CARD14*)Ribt}/Gt(ROSA)26Sor⁺; Malt1^{tm1c(EUCOMM)Hmgu}/Malt1^{tm1c(EUCOMM)Hmgu}; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NCrl * CD-1

integument

skin inflammation ( J:292094 )

• in tamoxifen-treated mice that is not as severe as in mice with wild-type Matl1

thick epidermis ( J:292094 )

• in tamoxifen-treated mice that is not as severe as in mice with wild-type Matl1

psoriasis ( J:292094 )

• from 6 weeks on, mice exhibit mild ear thickening unlike control mice

• tamoxifen-treated mice exhibit increased ear swelling that is not as severe as in mice with wild-type Matl1

immune system

increased neutrophil cell number ( J:292094 )

• in tamoxifen-treated mice that is not as severe as in mice with wild-type Matl1

increased dendritic cell number ( J:292094 )

• in tamoxifen-treated mice that is not as severe as in mice with wild-type Matl1

skin inflammation ( J:292094 )

• in tamoxifen-treated mice that is not as severe as in mice with wild-type Matl1

growth/size/body

decreased body weight ( J:292094 )

• in tamoxifen-treated that is not as severe as in mice with wild-type Matl1

hematopoietic system

increased neutrophil cell number ( J:292094 )

• in tamoxifen-treated mice that is not as severe as in mice with wild-type Matl1

increased dendritic cell number ( J:292094 )

• in tamoxifen-treated mice that is not as severe as in mice with wild-type Matl1

Genotype
MGI:6460073

cn16

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CARD14*)Ribt}/Gt(ROSA)26Sor⁺; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NCrl * CD-1

mortality/aging

premature death ( J:292094 )

• in tamoxifen-treated mice

integument

increased keratinocyte proliferation ( J:292094 )

• in the basal layer of ear skin of tamoxifen-treated mice

skin inflammation ( J:292094 )

• reminiscent of Munros abscesses in the stratum corneum in tamoxifen-treated mice

hyperkeratosis ( J:292094 )

• in tamoxifen-treated mice

parakeratosis ( J:292094 )

• in tamoxifen-treated mice

acanthosis ( J:292094 )

• in tamoxifen-treated mice

thick epidermis ( J:292094 )

• in tamoxifen-treated mice

psoriasis ( J:292094 )

• from 6 weeks on, mice exhibit mild ear thickening unlike control mice

• tamoxifen-treated mice exhibit increased progressive ear swelling with ears becoming scaly and red unlike control mice

immune system

increased neutrophil cell number ( J:292094 )

• in the ear of tamoxifen-treated mice

increased dendritic cell number ( J:292094 )

• in the ear of tamoxifen-treated mice

skin inflammation ( J:292094 )

• reminiscent of Munros abscesses in the stratum corneum in tamoxifen-treated mice

growth/size/body

decreased body weight ( J:292094 )

• in tamoxifen-treated mice

homeostasis/metabolism

decreased circulating glucose level ( J:292094 )

• in tamoxifen-treated mice

cellular

increased keratinocyte proliferation ( J:292094 )

• in the basal layer of ear skin of tamoxifen-treated mice

hematopoietic system

increased neutrophil cell number ( J:292094 )

• in the ear of tamoxifen-treated mice

increased dendritic cell number ( J:292094 )

• in the ear of tamoxifen-treated mice

Genotype
MGI:5289774

cn17

• Allelic Composition: Gt(ROSA)26Sor^tm1(DTA)Jpmb/Gt(ROSA)26Sor^tm1(DTA)Jpmb; Tg(KRT14-cre/ERT)20Efu/?
• Genetic Background: involves: 129S/SvEv * CD-1

digestive/alimentary system

abnormal stomach epithelium morphology ( J:173368 )

• treatment of mice with tamoxifen results in an expansion of Krt7-expressing cells from their ordered appearance at the squamocolumnar junction to more anterior regions of the proximal stomach; the migrating Krt7+ cells do not have squamous properties

Genotype
MGI:5645058

cn18

• Allelic Composition: Cebpa^tm1Gonz/Cebpa^tm1Gonz; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * CD-1

cellular

increased keratinocyte proliferation ( J:158721 )

• 4OHT-treated mutant mice show a significant increase in the number of BrdU positive basal keratinocytes relative to controls

integument

integument phenotype ( J:158721 )

N • 4OHT-treated mutant mice show no major changes in the morphology of interfollicular epidemis, outer root sheath of the hair follicle, and sebaceous glands relative to controls

N • normal IHC staining for K5, K10, loricrin and involucrin is observed in epidermis

increased keratinocyte proliferation ( J:158721 )

• 4OHT-treated mutant mice show a significant increase in the number of BrdU positive basal keratinocytes relative to controls

epidermal hyperplasia ( J:158721 )

• 4OHT-treated mutant mice show a significant increase in the number of nucleated cell layers relative to controls

thick epidermis ( J:158721 )

• 4OHT-treated mutant mice show a moderate increase in epidermal thickness relative to controls

Genotype
MGI:5478604

cn19

• Allelic Composition: Cdcp1^tm1.2Moas/Cdcp1^tm1.2Moas; Gt(ROSA)26Sor^{tm1(Smo/EYFP)Amc}/Gt(ROSA)26Sor⁺; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * CD-1 * FVB/N * SJL

mortality/aging

premature death ( J:194368 )

• euthanized 12 weeks after tamoxifen-treatment

integument

focal hair loss ( J:194368 )

• in tamoxifen-treated mice, particularly evident on the abdominal skin

abnormal skin morphology ( J:194368 )

• tamoxifen-treated mice develop more severe epidermal disease (thick skin, hair loss and scaling) compared with control mice

thick epidermis ( J:194368 )

• 3.5-fold in tamoxifen-treated mice than in control mice

abnormal skin condition ( J:194368 )

• in tamoxifen-treated mice, particularly evident on the abdominal skin

thick skin ( J:194368 )

• in tamoxifen-treated mice

neoplasm

increased tumor growth/size ( J:194368 )

• accelerated neoplasm development in tamoxifen-treated mice compared with control mice

increased tumor incidence ( J:194368 )

• accelerated neoplasm development in tamoxifen-treated mice compared with control mice

behavior/neurological

hunched posture ( J:194368 )

• in tamoxifen-treated mice

Genotype
MGI:5775156

cn20

• Allelic Composition: Ppp6c^tm1Shma/Ppp6c^tm1Shma; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: C57BL/6 * CBA * CD-1

integument

decreased subcutaneous adipose tissue amount ( J:231809 )

• in tamoxifen- and DMBA-treated mice

increased susceptibility to chemically induced skin inflammation ( J:231809 )

• cellular infiltration of the dermis in tamoxifen- and DMBA-treated mice

hyperkeratosis ( J:231809 )

• in tamoxifen- and DMBA-treated mice

thick epidermis ( J:231809 )

• in tamoxifen- and DMBA-treated mice

neoplasm

increased incidence of tumors by chemical induction ( J:231809 )

• tamoxifen-treated mice subjected to a DMBA and TPA skin cancer model exhibit earlier papilloma development compared with control mice

• tamoxifen-treated mice subjected to a DMBA and OA skin cancer model exhibit earlier papilloma development with a slight increase in tumor number compared with control mice

• tamoxifen-treated mice painted with DMBA exhibit increased skin tumor (hyperkeratotic papillomas, early follicular papilloma,exophytic papilloma, mixed papilloma, and fibropapilloma) formation compared with control mice

• however, the total number of tumors is not affected in the DMBA/TPA model

adipose tissue

decreased subcutaneous adipose tissue amount ( J:231809 )

• in tamoxifen- and DMBA-treated mice

immune system

increased susceptibility to chemically induced skin inflammation ( J:231809 )

• cellular infiltration of the dermis in tamoxifen- and DMBA-treated mice

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:231809 )

• tamoxifen-treated mice subjected to a DMBA and TPA skin cancer model exhibit earlier papilloma development compared with control mice

• tamoxifen-treated mice subjected to a DMBA and OA skin cancer model exhibit earlier papilloma development with a slight increase in tumor number compared with control mice

• tamoxifen-treated mice painted with DMBA exhibit increased skin tumor (hyperkeratotic papillomas, early follicular papilloma,exophytic papilloma, mixed papilloma, and fibropapilloma) formation compared with control mice

• however, the total number of tumors is not affected in the DMBA/TPA model

Genotype
MGI:3851141

cn21

• Allelic Composition: Cul4a^tm1.1Pz/Cul4a^tm1.1Pz; Tg(KRT14-cre/ERT)20Efu/?
• Genetic Background: involves: C57BL/6 * CD-1

neoplasm

decreased incidence of tumors by UV induction ( J:150427 )

• mice with cre induction in the skin are highly resistant to UVB induced tumors in the skin

• by 48 weeks of UVB treatmeant, all wild-type mice have developed squamous cell carcinomas while only 1 of 13 mutant mice have developed tumors

Genotype
MGI:6277933

cn22

• Allelic Composition: Lama3^tm1Arte/Lama3^tm1Arte; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: C57BL/6 * CD-1

growth/size/body

decreased body size ( J:240054 )

• mice fed a tamoxifen-containing diet are slightly smaller after 10-11 weeks on tamoxifen

integument

skin inflammation ( J:240054 )

• blisters of tamoxifen-treated mice are associated with an inflammatory reaction in the dermis, with accumulation of myofibroblasts, granulocytes and macrophages in the repair tissue filling the blisters and accumulating below blisters

• blister cavities are filled with eosinophil-rich material in some areas

abnormal nail morphology ( J:240054 )

• mice are losing their nails after 10-11 weeks of tamoxifen treatment and most nails are lost after 15-16 weeks of tamoxifen

abnormal hair follicle orientation ( J:240054 )

• hair follicles tend to be perpendicular to the skin surface in tamoxifen-treated mice rather than the oblique/tilted orientation seen in controls

dermal-epidermal separation ( J:240054 )

• skin shows sporadic detachment between epidermis and dermis starting not earlier than 8 weeks after beginning tamoxifen treatment and blisters are present in back skin of all mice after 10-15 weeks, with extensive detachment of the entire interfollicular epidermis from the dermis and increased dermal cellularity

bleb ( J:240054 )

• tamoxifen-treated mice have bullae on the footpads

blistering ( J:240054 )

• mice start to develop blisters and erosions on the footpads around 10-11 weeks after the onset of tamoxifen-containing diet and exhibit scabs under the paws after 15-16 weeks of tamoxifen

• mice show blister formation below the interfollicular epidermis following tamoxifen treatment

thick skin ( J:240054 )

• integument is thicker in tamoxifen-treated mice

skin fibrosis ( J:240054 )

• blisters are associated with an accumulation of fibrillar collagens in tamoxifen-treated mice indicating skin fibrosis

homeostasis/metabolism

increased collagen level ( J:240054 )

• tamoxifen-treated mice show accumulation of collagen in the dermis

immune system

skin inflammation ( J:240054 )

• blisters of tamoxifen-treated mice are associated with an inflammatory reaction in the dermis, with accumulation of myofibroblasts, granulocytes and macrophages in the repair tissue filling the blisters and accumulating below blisters

• blister cavities are filled with eosinophil-rich material in some areas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
junctional epidermolysis bullosa		DOID:3209		J:240054

Genotype
MGI:5544607

cn23

• Allelic Composition: Trpv4^tm1.1Ldtk/Trpv4^tm1.1Ldtk; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: C57BL/6 * CD-1 * SJL

Tamoxifen-treated Trpv4^tm1.1Ldtk/Trpv4^tm1.1Ldtk Tg(KRT14-cre/ERT)20Efu/0 mice show protection from UVB-induced tissue injury

behavior/neurological

behavior/neurological phenotype ( J:200749 )

N • chemical irritant-induced nocifensive behavior is similar to controls

abnormal mechanical nociception ( J:200749 )

• decrease in sensitivity toward noxious mechanical stimulation 48 hours after UV exposure compared to similarly treated controls

increased thermal nociceptive threshold ( J:200749 )

• decrease in sensitivity toward noxious radiant heat stimulation in tamoxifen treated mice 48 hours after UV exposure compared to similarly treated controls

integument

abnormal skin physiology ( J:200749 )

• no signs of UVB-induced tissue injury are seen in tamoxifen treated mice with complete targeting

• UVB-induced tissue injury maybe moderately less severe in tamoxifen treated mice with incomplete targeting

Genotype
MGI:5804631

cn24

• Allelic Composition: Sod2^tm1Smel/Sod2^tm1Smel; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: C57BL/6J * CD-1

homeostasis/metabolism

delayed wound healing ( J:226565 )

• after a skin biopsy, 14-mo-old mice treated with TAM at 4 months show delayed wound closure relative to vehicle-treated mice

• faster wound closure noted in 8-mo-old mice is lost at 11 months of age (i.e. at 7 months after TAM treatment)

enhanced wound healing ( J:226565 )

• 8-mo-old mice treated with TAM at 4 months show accelerated wound closure after a skin biopsy relative to vehicle-treated mice

• young TAM-treated mice show an unusually thick layer of epidermal cells near the wound edges but no difference in collagen formation, suggesting rapid re-epithelialization

• faster wound closure in young TAM-treated mice is likely due to a transient increase in epidermal differentiation, rather than increased cell proliferation

cellular

abnormal keratinocyte differentiation ( J:226565 )

• at 6 days after skin injury, wounds in young TAM-treated mice show a few cells in the stratum basale (SB) layer and a prominent stratum granulosum (SG) layer, suggesting accelerated epidermal differentiation during wound healing

• however, acceleration is only transient, as no difference in epidermal stratification is noted between young TAM- and vehicle-treated mice at 10 days after injury

decreased keratinocyte proliferation ( J:226565 )

• whereas TPA treatment enhances epidermal proliferation in vehicle-treated mice, TPA induces less proliferation in the epidermis of 8-mo-old mice pretreated with TAM at 4 months, as determined by Ki67 staining

early cellular replicative senescence ( J:226565 )

• 8-mo-old mice treated with TAM at 4 months show a 2.5-fold higher senescence-associated beta-galactosidase activity in the epidermis relative to vehicle treated mice; staining is more evident in the stratum corneum or more differentiated layers

• epidermal p16^INK4a mRNA is detectable in most (>70%) skin samples at 4 months and even at 10 months after TAM treatment

abnormal mitochondrial ATP synthesis coupled electron transport ( J:226565 )

• 8-mo-old mice treated with TAM at 4 months show significantly less succinate dehydrogenase (complex II) activity in epidermis/hair follicles, but not in skeletal muscle beneath the stratum corneum layer, relative to vehicle-treated mice

• however, mitochondrial complex IV (COX) activity is similar in TAM- and vehicle-treated mice

integument

abnormal keratinocyte differentiation ( J:226565 )

• at 6 days after skin injury, wounds in young TAM-treated mice show a few cells in the stratum basale (SB) layer and a prominent stratum granulosum (SG) layer, suggesting accelerated epidermal differentiation during wound healing

• however, acceleration is only transient, as no difference in epidermal stratification is noted between young TAM- and vehicle-treated mice at 10 days after injury

decreased keratinocyte proliferation ( J:226565 )

• whereas TPA treatment enhances epidermal proliferation in vehicle-treated mice, TPA induces less proliferation in the epidermis of 8-mo-old mice pretreated with TAM at 4 months, as determined by Ki67 staining

abnormal epidermis stratum corneum morphology ( J:226565 )

• TPA treatment causes stratum corneum (SC) separation in 8-mo-old mice pretreated with TAM at 4 months of age

thick epidermis ( J:226565 )

• after a skin biopsy, 8-mo-old mice treated with TAM at 4 months show an unusually thick layer of epidermal cells near the wound edges relative to vehicle-treated mice

thin epidermis ( J:226565 )

• TAM-treated mice exhibit faster age-related epidermal thinning with a significant decline in epidermal thickness at 7 months after TAM treatment, whereas vehicle-treated mice show epidermal thinning after 10 months of vehicle treatment

• TPA (12-O-tetradecanoylphorbol-13-acetate) treatment fails to promote epidermal thickening in TAM-treated mice, unlike in vehicle-treated mice

skin lesions ( J:226565 )

• TPA treatment causes epidermal lesions in 8-mo-old mice pretreated with TAM at 4 months of age

decreased epidermal stem cell number ( J:226565 )

• 14-mo-old mice treated with TAM at 4 months show a marked reduction in epidermal bulge stem cells (CD49f^hi/CD34⁺), suprabasal bulge stem cells (CD49f^lo/CD34⁺), and junctional zone stem cells (CD49f^hi/CD34^-/Sca1^-) relative to vehicle-treated mice, indicating epidermal stem cell exhaustion