Phenotypes associated with this allele

• Allele Symbol: Tg(KRT14-rtTA)F42Efu
• Allele Name: transgene insertion F42, Elaine Fuchs
• Allele ID: MGI:3762564
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Notch1^tm2Rko/Notch1^tm2Rko Tg(KRT14-rtTA)F42Efu/0 Tg(tetO-cre)1Jaw/0	involves: 129 * 129X1/SvJ * C57BL/6 * FVB/N	MGI:5512989
cn2	Gt(ROSA)26Sor^tm1(MAML1)Wsp/Gt(ROSA)26Sor^+ Tg(KRT14-rtTA)F42Efu/0 Tg(tetO-cre)1Jaw/0	involves: 129 * C57BL/6 * FVB	MGI:5512988
cn3	Mc1r^tm1.1Mymi/Mc1r^tm1.1Mymi Tg(KRT14-rtTA)F42Efu/0 Tg(tetO-EDN1,-lacZ)9Mhus/0 Tg(Tyr-cre/ERT2)13Bos/0	involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NTac * FVB	MGI:6269451
cn4	Ctnnb1^tm2Kem/Ctnnb1^tm2Kem Tg(KRT14-rtTA)F42Efu/0 Tg(tetO-EDN1,-lacZ)9Mhus/0 Tg(Tyr-cre/ERT2)13Bos/0	involves: C57BL/6J * FVB	MGI:6269417
cn5	Tg(KRT14-rtTA)F42Efu/0 Tg(tetO-EDN1,-lacZ)9Mhus/0	involves: C57BL/6J * FVB	MGI:6269409
cx6	Tg(KRT14-rtTA)F42Efu/0 Tg(tetO-Tcf3)1Efu/0	involves: FVB	MGI:3762587
cx7	Tg(tetO-Mir24-1)#Smoc/0 Tg(KRT14-rtTA)F42Efu/0	involves: FVB	MGI:6726111
cx8	Tg(KRT14-rtTA)F42Efu/0 Tg(tetO-GJB2*G45E,-EGFP)#Tww/0	involves: FVB/N * SKH1	MGI:5635532
tg9	Tg(KRT14-rtTA)F42Efu/0	involves: FVB	MGI:3762588

Genotype
MGI:5512989

cn1

• Allelic Composition: Notch1^tm2Rko/Notch1^tm2Rko; Tg(KRT14-rtTA)F42Efu/0; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129 * 129X1/SvJ * C57BL/6 * FVB/N

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

vision/eye

Meibomian gland degeneration ( J:194073 )

• mutants treated with doxycycline from P1 to P16 show degeneration of ocular glands, including lacrimal and Meibomian glands

lacrimal gland degeneration ( J:194073 )

• mutants treated with doxycycline from P1 to P16 show degeneration of ocular glands, including lacrimal and Meibomian glands

decreased conjunctiva goblet cell number ( J:194073 )

• mutants treated with doxycycline from P1 to P16 exhibit loss of conjunctival goblet cells

dry eyes ( J:194073 )

• mutants treated with doxycycline from P1 to P16 have poor tear volume

endocrine/exocrine glands

Meibomian gland degeneration ( J:194073 )

• mutants treated with doxycycline from P1 to P16 show degeneration of ocular glands, including lacrimal and Meibomian glands

lacrimal gland degeneration ( J:194073 )

• mutants treated with doxycycline from P1 to P16 show degeneration of ocular glands, including lacrimal and Meibomian glands

integument

Meibomian gland degeneration ( J:194073 )

• mutants treated with doxycycline from P1 to P16 show degeneration of ocular glands, including lacrimal and Meibomian glands

alopecia ( J:194073 )

• mutants treated with doxycycline from P1 to P16 show hair loss on the skin and eyelids

Genotype
MGI:5512988

cn2

• Allelic Composition: Gt(ROSA)26Sor^{tm1(MAML1)Wsp}/Gt(ROSA)26Sor⁺; Tg(KRT14-rtTA)F42Efu/0; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129 * C57BL/6 * FVB

vision/eye

conjunctivitis ( J:194073 )

• CD45+ leukocyte infiltration is seen in the sub-conjunctival stroma 3-4 days after eyelid opening, at P16, of pups treated with doxycycline

abnormal eye morphology ( J:194073 )

• epithelial cells of the ocular surface of pups treated with doxycycline (via nursing moms) are hyperplastic and aberrantly desquamated from the conjunctiva

cornea vascularization ( J:194073 )

• pulse doxycycline induction from P0 to P16 results in mutants with severe ulceration and neovascularization in the cornea, even after 180 days post-doxycycline induction

abnormal conjunctival epithelium morphology ( J:194073 )

• the aberrantly desquamated cells within the conjunctival sac are composed of conjunctival epithelial cells and basal cells of stratified epithelia but not corneal epithelial cells, indicating aberrant conjunctival, but not corneal, epithelial cell desquamation

• conjunctival epithelia from pups treated with doxycycline (via nursing moms) exhibit an increase in cell proliferation

abnormal conjunctiva goblet cell differentiation ( J:194073 )

• pups treated with doxycycline (via nursing moms) do not show signs of goblet cell differentiation from the conjunctival epithelium at P9 or P16 unlike controls

decreased conjunctiva goblet cell number ( J:194073 )

• adult mice administered doxycycline at P90 exhibit loss of goblet cells from the conjunctiva and cellular debris in the conjunctival sac

abnormal conjunctival sac morphology ( J:194073 )

• pups from nursing moms administered doxycycline do not exhibit clear conjunctival sacs at P9 as in wild-type pups and instead have a mass of cell debris that is abnormally present in the conjunctival sac, indicating early ocular surface morphogenesis alterations

• adult mice administered doxycycline at P90 exhibit cellular debris in the conjunctival sac

abnormal cornea epithelium morphology ( J:194073 )

• pups treated with doxycycline exhibit epidermal metaplasia of corneal epithelium at P16

cornea ulcer ( J:194073 )

• pulse doxycycline induction from P0 to P16 results in mutants with severe ulceration and neovascularization in the cornea, even after 180 days post-doxycycline induction

cardiovascular system

cornea vascularization ( J:194073 )

• pulse doxycycline induction from P0 to P16 results in mutants with severe ulceration and neovascularization in the cornea, even after 180 days post-doxycycline induction

immune system

conjunctivitis ( J:194073 )

• CD45+ leukocyte infiltration is seen in the sub-conjunctival stroma 3-4 days after eyelid opening, at P16, of pups treated with doxycycline

integument

alopecia ( J:194073 )

• adult mice administered doxycycline at P90, exhibit hair loss one month after doxycycline induction, with random alopecia on the body, including the eyelid within 3 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
keratoconjunctivitis sicca		DOID:12895		J:194073

Genotype
MGI:6269451

cn3

• Allelic Composition: Mc1r^tm1.1Mymi/Mc1r^tm1.1Mymi; Tg(KRT14-rtTA)F42Efu/0; Tg(tetO-EDN1,-lacZ)9Mhus/0; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NTac * FVB

pigmentation

abnormal epidermal melanocyte morphology ( J:231435 )

• following wounding, mice show a significant increase of epidermal melanocytes containing dark pigment in the wound site, indicating that Edn1 overexpression in epithelial cells can rescue the defect of epidermal melanocyte regeneration caused by MC1R loss in the melanocyte lineage

integument

abnormal epidermal melanocyte morphology ( J:231435 )

• following wounding, mice show a significant increase of epidermal melanocytes containing dark pigment in the wound site, indicating that Edn1 overexpression in epithelial cells can rescue the defect of epidermal melanocyte regeneration caused by MC1R loss in the melanocyte lineage

Genotype
MGI:6269417

cn4

• Allelic Composition: Ctnnb1^tm2Kem/Ctnnb1^tm2Kem; Tg(KRT14-rtTA)F42Efu/0; Tg(tetO-EDN1,-lacZ)9Mhus/0; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: C57BL/6J * FVB

pigmentation

abnormal melanocyte differentiation ( J:231435 )

• following depletion of beta-catenin in McSCs during anagen, McSCs fail to differentiate as shown by the absence of pigment and Tyr expression in McSCs at anagen onset

abnormal melanocyte proliferation ( J:231435 )

• following depletion of beta-catenin in McSCs during anagen, McSCs fail to proliferate as shown by the absence of Ki67 expression in McSCs at anagen onset; this is in contrast to control littermates that overexpress Edn1 with intact Wnt signaling

abnormal coat/hair pigmentation ( J:231435 )

• following depletion of beta-catenin in McSCs during anagen, mice develop a hair-graying phenotype by the 2nd telogen; this is in contrast to control littermates that overexpress Edn1 with intact Wnt signaling

abnormal epidermal melanocyte morphology ( J:231435 )

• following depletion of beta-catenin in McSCs during anagen, wounded mice show a significant reduction in the number of epidermal melanocytes relative to control littermates that overexpress Edn1 with intact Wnt signaling

integument

abnormal coat/hair pigmentation ( J:231435 )

• following depletion of beta-catenin in McSCs during anagen, mice develop a hair-graying phenotype by the 2nd telogen; this is in contrast to control littermates that overexpress Edn1 with intact Wnt signaling

abnormal epidermal melanocyte morphology ( J:231435 )

• following depletion of beta-catenin in McSCs during anagen, wounded mice show a significant reduction in the number of epidermal melanocytes relative to control littermates that overexpress Edn1 with intact Wnt signaling

cellular

abnormal melanocyte differentiation ( J:231435 )

• following depletion of beta-catenin in McSCs during anagen, McSCs fail to differentiate as shown by the absence of pigment and Tyr expression in McSCs at anagen onset

abnormal melanocyte proliferation ( J:231435 )

• following depletion of beta-catenin in McSCs during anagen, McSCs fail to proliferate as shown by the absence of Ki67 expression in McSCs at anagen onset; this is in contrast to control littermates that overexpress Edn1 with intact Wnt signaling

Genotype
MGI:6269409

cn5

• Allelic Composition: Tg(KRT14-rtTA)F42Efu/0; Tg(tetO-EDN1,-lacZ)9Mhus/0
• Genetic Background: involves: C57BL/6J * FVB

pigmentation

pigmentation phenotype ( J:231435 )

N • following induction of Edn1 expression with Dox treatment during anagen, mice exhibit no premature hair graying phenotype at least by the 4th telogen

abnormal melanocyte differentiation ( J:231435 )

• following induction with Dox during anagen, mice continue to have Tyr+ melanocytes in the melanocyte stem cell (McSC) niche by anagen IV, unlike control mice where Tyr immunoreactivity is reduced after departure of differentiated melanocytes toward the hair bulb, indicating increased differentiation of McSCs during hair follicle regeneration

• however, the number of McSCs is maintained at least by the 4th telogen

abnormal melanocyte proliferation ( J:231435 )

• following induction with Dox during anagen, mice show a significant increase in McSC proliferation at anagen onset (anagen I/II) but not at later anagen stages (IV/V); only McSCs with nuclear beta-catenin signal (indicating Wnt activation) show increased proliferation activity at anagen onset

• following Dox treatment immediately after wounding at 8 weeks of age, McSCs found in the bulge, upper hair follicle, and inter-follicular epidermis show significantly higher proliferation activity than those in control mice; after injury, actively proliferating melanocytes express nuclear beta-catenin, whereas cells lacking Wnt activation show no proliferation

ectopic hair follicle melanin granules ( J:231435 )

• following induction with Dox treatment during anagen, mice show ectopic pigmentation in the bulge/secondary hair germ (sHG) area of hair follicles at anagen onset (anagen I/II), whereas control mice lack pigmentation in this area

• ectopic pigmentation persists in this niche through later stages of anagen

abnormal epidermal melanocyte morphology ( J:231435 )

• following Dox treatment immediately after wounding at 8 weeks of age, mice show a dramatic increase of epidermal melanocyte number in the wound area at day 8 after re- epithelialization relative to control mice; unexpectedly, all de novo hair follicles produce pigmented hair, unlike in control mice

• unwounded adult mice treated with Dox during anagen show a significant increase of pigmented melanocytes in interfollicular epidermis by 12 days after induction, indicating enhanced upward migration of McSCs from the hair follicle to the epidermis in the absence of wounding; in contrast, upon induction with Dox during telogen epidermal melanocytes remain undetectable

integument

ectopic hair follicle melanin granules ( J:231435 )

• following induction with Dox treatment during anagen, mice show ectopic pigmentation in the bulge/secondary hair germ (sHG) area of hair follicles at anagen onset (anagen I/II), whereas control mice lack pigmentation in this area

• ectopic pigmentation persists in this niche through later stages of anagen

abnormal epidermal melanocyte morphology ( J:231435 )

• following Dox treatment immediately after wounding at 8 weeks of age, mice show a dramatic increase of epidermal melanocyte number in the wound area at day 8 after re- epithelialization relative to control mice; unexpectedly, all de novo hair follicles produce pigmented hair, unlike in control mice

• unwounded adult mice treated with Dox during anagen show a significant increase of pigmented melanocytes in interfollicular epidermis by 12 days after induction, indicating enhanced upward migration of McSCs from the hair follicle to the epidermis in the absence of wounding; in contrast, upon induction with Dox during telogen epidermal melanocytes remain undetectable

cellular

abnormal melanocyte differentiation ( J:231435 )

• following induction with Dox during anagen, mice continue to have Tyr+ melanocytes in the melanocyte stem cell (McSC) niche by anagen IV, unlike control mice where Tyr immunoreactivity is reduced after departure of differentiated melanocytes toward the hair bulb, indicating increased differentiation of McSCs during hair follicle regeneration

• however, the number of McSCs is maintained at least by the 4th telogen

abnormal melanocyte proliferation ( J:231435 )

• following induction with Dox during anagen, mice show a significant increase in McSC proliferation at anagen onset (anagen I/II) but not at later anagen stages (IV/V); only McSCs with nuclear beta-catenin signal (indicating Wnt activation) show increased proliferation activity at anagen onset

• following Dox treatment immediately after wounding at 8 weeks of age, McSCs found in the bulge, upper hair follicle, and inter-follicular epidermis show significantly higher proliferation activity than those in control mice; after injury, actively proliferating melanocytes express nuclear beta-catenin, whereas cells lacking Wnt activation show no proliferation

Genotype
MGI:3762587

cx6

• Allelic Composition: Tg(KRT14-rtTA)F42Efu/0; Tg(tetO-Tcf3)1Efu/0
• Genetic Background: involves: FVB

endocrine/exocrine glands

abnormal sebocyte differentiation ( J:116057 )

• induction of Tcf3 beginning on P1 impairs the end stage of sebaceous gland differentiation

decreased sebocyte cell number ( J:116057 )

• 48 hours after doxycycline treatment, numbers of sebocytes are reduced

absent sebocyte ( J:116057 )

• by 4 days of doxycycline administration, sebocytes are no longer detected

digestive/alimentary system

abnormal tongue epithelium morphology ( J:116057 )

• when pregnant double transgenic mice are administered doxycycline when the embryos are E13.5, epidermal differentiation in the tongue of pups is significantly impaired when examined at P1; the differentiation marker loricrin is reduced in the epithelium, while the simple epithelial marker K8 shows significant induction of expression

craniofacial

abnormal tongue epithelium morphology ( J:116057 )

• when pregnant double transgenic mice are administered doxycycline when the embryos are E13.5, epidermal differentiation in the tongue of pups is significantly impaired when examined at P1; the differentiation marker loricrin is reduced in the epithelium, while the simple epithelial marker K8 shows significant induction of expression

integument

abnormal sebocyte differentiation ( J:116057 )

• induction of Tcf3 beginning on P1 impairs the end stage of sebaceous gland differentiation

decreased sebocyte cell number ( J:116057 )

• 48 hours after doxycycline treatment, numbers of sebocytes are reduced

absent sebocyte ( J:116057 )

• by 4 days of doxycycline administration, sebocytes are no longer detected

abnormal hair follicle development ( J:116057 )

• after induction of Tcf3 with doxycycline treatment beginning on P1, hair follicle maturation is impaired; follicle downgrowth appears to arrest with Tcf3 induction

abnormal hair cycle ( J:116057 )

• when skin from doxycycline-treated P transgenic is transplanted onto control mice, by day 27 specified follicles have undergone degeneration and fail to reenter the hair cycle

• epidermis and residual established hair follicles in grafts have developed into large masses of undifferentiated epithelial cells lacking all markers of epidermal terminal differentiation

abnormal epidermal layer morphology ( J:116057 )

• keratohyalin granules, loricrin, and involucrin are dramatically reduced within 4 days of doxycycline administration starting on P1

• flattened squames are present at the skin surface; these appear to be dead keratinocytes

abnormal epidermis stratum spinosum morphology ( J:116057 )

• within 4 days of doxycycline administration starting on P1, thick filament bundles characteristic of spinous layer K1/K10 filaments are barely detectable

abnormal skin development ( J:116057 )

• epidermal differentiation is severely diminished within 4 days of doxycycline administration (resulting in Tcf3 induction) starting at postnatal day 1

growth/size/body

abnormal tongue epithelium morphology ( J:116057 )

• when pregnant double transgenic mice are administered doxycycline when the embryos are E13.5, epidermal differentiation in the tongue of pups is significantly impaired when examined at P1; the differentiation marker loricrin is reduced in the epithelium, while the simple epithelial marker K8 shows significant induction of expression

Genotype
MGI:6726111

cx7

• Allelic Composition: Tg(tetO-Mir24-1)#Smoc/0; Tg(KRT14-rtTA)F42Efu/0
• Genetic Background: involves: FVB

mortality/aging

prenatal lethality, incomplete penetrance ( J:306624 )

• fewer than expected mice are born when pups are exposed to doxycycline from E11

integument

decreased keratinocyte proliferation ( J:306624 )

• in the interfollicular epidermis at E15 in doxycycline-treated mice from E13

abnormal hair growth ( J:306624 )

• mice fail to grow hair in response to 3% minoxidil treatment unlike wild-type mice

abnormal hair cycle anagen phase ( J:306624 )

• delayed initiation in doxycycline-treated mice

thin epidermis ( J:306624 )

• thin interfollicular epidermis in doxycycline-treated mice

abnormal skin development ( J:306624 )

• immature skin in doxycycline-treated mice

growth/size/body

decreased body size ( J:306624 )

• at P3 in doxycycline-treated mice

cellular

decreased keratinocyte proliferation ( J:306624 )

• in the interfollicular epidermis at E15 in doxycycline-treated mice from E13

Genotype
MGI:5635532

cx8

• Allelic Composition: Tg(KRT14-rtTA)F42Efu/0; Tg(tetO-GJB2*G45E,-EGFP)#Tww/0
• Genetic Background: involves: FVB/N * SKH1

cellular

increased hair follicle apoptosis ( J:220589 )

• increase in apoptosis is seen in head skin, particularly in the thickened hair follicle epithelium after 3 weeks of doxycycline treatment

mortality/aging

postnatal lethality, incomplete penetrance ( J:220589 )

• mortality rate is greater than 50% by weaning when transgene expression is induced in utero with doxycycline and surviving mice are in poor health

• mice raised without doxycycline exhibit normal postnatal development and lifespan

growth/size/body

decreased body size ( J:220589 )

• neonates that had been induced with doxycycline in utero are reduced in size

endocrine/exocrine glands

sebaceous gland atrophy ( J:220589 )

• sebaceous gland atrophy after 10 weeks of doxycycline treatment

integument

increased hair follicle apoptosis ( J:220589 )

• increase in apoptosis is seen in head skin, particularly in the thickened hair follicle epithelium after 3 weeks of doxycycline treatment

sebaceous gland atrophy ( J:220589 )

• sebaceous gland atrophy after 10 weeks of doxycycline treatment

abnormal hair follicle morphology ( J:220589 )

• extensive hair follicle atrophy after 10 weeks of doxycycline treatment

abnormal skin morphology ( J:220589 )

• adult mice develop skin abnormalities within 7-14 days of doxycycline induction; skin pathology worsens when mice are maintained on doxycycline for longer periods

• mice induced with doxycycline for 4 weeks show greater undulation of the epidermis into the dermis (papillomatosis)

abnormal dermal layer morphology ( J:220589 )

• subepidermal dermis shows elongated and dilated capillaries and a mild lymphocytic infiltration in mice induced with doxycycline for 4 weeks

• increase in apoptosis is seen in head skin, particularly in the dermis after 3 weeks of doxycycline treatment

abnormal epidermal layer morphology ( J:220589 )

• increase in number of mitotic epidermal cells in mice induced with doxycycline for 4 weeks

abnormal epidermis stratum corneum morphology ( J:220589 )

• mice induced with doxycycline for 4 weeks show a thickened and compact but orthokeratotic stratum corneum

hyperkeratosis ( J:220589 )

• the hair follicle epithelium is hyperkeratotic in mice induced with doxycycline for 4 weeks show, leading to horny cysts and follicular plugging

• epidermis shows a massive hyperkeratosis with frequent keratotic plugging after 10 weeks of doxycycline treatment

orthokeratosis ( J:220589 )

• seen in mice induced with doxycycline for 4 weeks

acanthosis ( J:220589 )

• mice induced with doxycycline for 4 weeks show acanthosis

• the hair follicle epithelium is acanthotic in mice induced with doxycycline for 4 weeks

abnormal keratinocyte morphology ( J:220589 )

• keratinocytes are increased in size in mice treated with doxycycline, showing a 28% increase in cell perimeter

thick epidermis ( J:220589 )

• after 10 weeks of doxycycline treatment, mice exhibit extensively thickened epidermis

reddish skin ( J:220589 )

• neonates that had been induced with doxycycline in utero are reddish in appearance

scaly skin ( J:220589 )

• adult mice treated with doxycycline exhibit erythrokeratoderma and epidermal scaling

wrinkled skin ( J:220589 )

• after 10 weeks of doxycycline treatment, mice exhibit depended skin folds with a rough, coarse-grained appearance

abnormal keratinocyte physiology ( J:220589 )

• keratinocytes isolated from mice treated with doxycycline show increased whole-cell membrane currents at both hyperpolarizing and depolarizing membrane potentials

• membrane capacitance of keratinocytes from mice treated with doxycycline is increased

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal dominant keratitis-ichthyosis-deafness syndrome		DOID:0060871	OMIM:148210	J:220589

Genotype
MGI:3762588

tg9

• Allelic Composition: Tg(KRT14-rtTA)F42Efu/0
• Genetic Background: involves: FVB

normal phenotype

no abnormal phenotype detected ( J:116057 )

• hemizygotes are viable, fertile, and normal in size; mice do not display any gross physical or behavioral abnormalities