Phenotypes associated with this allele

• Allele Symbol: Tg(KRT5-tTA)1216Glk
• Allele Name: transgene insertion 1216, Adam Glick
• Allele ID: MGI:3575755
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(KRT5-tTA)1216Glk/0 Tg(tetO-Il13)1Tazh/0	B6.Cg-Tg(KRT5-tTA)1216Glk Tg(tetO-Il13)1Tazh	MGI:3850190
cx2	Tg(KRT5-tTA)1216Glk/0 Tg(tetO-Tek)1Dmt/0	involves: CD-1 * FVB/N	MGI:3842959
cx3	Tg(KRT5-tTA)1216Glk/0 Tg(tetO-TGFB1*C223S*C225S)1Glk/0	involves: FVB/N	MGI:3815534
cx4	Tg(KRT5-tTA)1216Glk/0 Tg(tetO-LMNA*G608G,-EGFP)VF1-07Maer/0	involves: FVB/N	MGI:3834667
cx5	Tg(KRT5-tTA)1216Glk/0 Tg(tetO-LMNA,-EGFP)SF1-04Maer/0	involves: FVB/N	MGI:3834668

Genotype
MGI:3850190

cx1

• Allelic Composition: Tg(KRT5-tTA)1216Glk/0; Tg(tetO-Il13)1Tazh/0
• Genetic Background: B6.Cg-Tg(KRT5-tTA)1216Glk Tg(tetO-Il13)1Tazh

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

immune system

cutaneous mastocytosis ( J:150232 )

• 4-fold in the skin following doxycycline withdrawal

increased IgE level ( J:150232 )

• following doxycycline withdrawal

increased IgG1 level ( J:150232 )

• following doxycycline withdrawal

increased interleukin-13 secretion ( J:150232 )

• following doxycycline withdrawal and stimulation with anti-CD3/CD28, lymphocytes and peripheral blood mononuclear cells produce more IL13 than wild-type cells

increased interleukin-4 secretion ( J:150232 )

• following doxycycline withdrawal, IL4 lymphocyte production is increased compared to in wild-type mice

dermatitis ( J:150232 )

• following doxycycline withdrawal, mice exhibit increased numbers of mononuclear cells and eosinophils infiltrating the subepidermal, intradermal, and perivascular spaces of the skin unlike in wild-type mice

cardiovascular system

increased angiogenesis ( J:150232 )

• following doxycycline withdrawal, mice exhibit an increase in subcutaneous blood vessel formation compared to in wild-type mice

hematopoietic system

cutaneous mastocytosis ( J:150232 )

• 4-fold in the skin following doxycycline withdrawal

increased IgE level ( J:150232 )

• following doxycycline withdrawal

increased IgG1 level ( J:150232 )

• following doxycycline withdrawal

homeostasis/metabolism

epidermal spongiosis ( J:150232 )

• spongiosis following doxycycline withdrawal

integument

dermatitis ( J:150232 )

• following doxycycline withdrawal, mice exhibit increased numbers of mononuclear cells and eosinophils infiltrating the subepidermal, intradermal, and perivascular spaces of the skin unlike in wild-type mice

alopecia ( J:150232 )

• following doxycycline withdrawal

thick dermal layer ( J:150232 )

• following doxycycline withdrawal

hyperkeratosis ( J:150232 )

• following doxycycline withdrawal

thick epidermis ( J:150232 )

• following doxycycline withdrawal

reddish skin ( J:150232 )

• following doxycycline withdrawal

skin lesions ( J:150232 )

• following doxycycline withdrawal, skin lesions progress and become extensive including dry lichenified skin lesions unlike in wild-type mice

abnormal skin condition ( J:150232 )

• following doxycycline withdrawal, mice exhibit skin crusting, excoriation, bacterial pyoderma, and erosions in the skin mostly on the back and abdominal areas unlike wild-type mice

epidermal spongiosis ( J:150232 )

• spongiosis following doxycycline withdrawal

skin fibrosis ( J:150232 )

• following doxycycline withdrawal, mice develop skin fibrosis unlike wild-type mice

increased pruritus ( J:150232 )

• following doxycycline withdrawal, mice exhibit pruritus unlike wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
atopic dermatitis		DOID:3310	OMIM:603165 OMIM:PS603165	J:150232

Genotype
MGI:3842959

cx2

• Allelic Composition: Tg(KRT5-tTA)1216Glk/0; Tg(tetO-Tek)1Dmt/0
• Genetic Background: involves: CD-1 * FVB/N

immune system

increased interferon-gamma secretion ( J:147438 )

• is increased in the ear and back skin of mice

abnormal interleukin secretion ( J:147438 )

• interleukin-22 secretion is increased in the ear and back skin of mice

increased interleukin-12 secretion ( J:147438 )

• is increased in the ear and back skin of mice

increased interleukin-17 secretion ( J:147438 )

• is increased in the ear and back skin of mice

increased interleukin-23 secretion ( J:147438 )

• is increased in the ear and back skin of mice

skin inflammation ( J:147438 )

• inflammatory infiltrate associated with psoriasis includes CD4⁺ T cells in the dermis and CD8⁺ T cells in the epidermis, myeloid dendritic cells, macrophages and granulocytes

cardiovascular system

abnormal vascular branching morphogenesis ( J:147438 )

• mouse ears by 21 days of age contain larger blood vessels that are more highly branched

• a similar trend is observed for vessels in both dorsal and ventral superficial fascia

increased angiogenesis ( J:147438 )

• ears contain 59% more blood vessels and back skin 102% more blood vessels than controls

integument

skin inflammation ( J:147438 )

• inflammatory infiltrate associated with psoriasis includes CD4⁺ T cells in the dermis and CD8⁺ T cells in the epidermis, myeloid dendritic cells, macrophages and granulocytes

acanthosis ( J:147438 )

• is observed in the skin and back

reddish skin ( J:147438 )

• mouse ears are erythematous by 21 days of age

psoriasis ( J:147438 )

• skin begins to develop reddened, scaly, hyperkeratotic lesions between 2 to 6 months of age

• lesions involve hyperplasia of the epidermis, a loss of the granular cell layer, thickening of the interfollicular epidermal layers, confluent parakeratotic scale, increased dermal angiogenesis, and extensive inflammatory infiltration

• dorsal and ventral surfaces, bilateral elbows, and skin surrounding the genital region can develop these lesion

• 73% of mice have lesions involving back and ear, 22% develop just ear lesions, and 5% develop no lesions

• psoriasis can be reversed by treatment with doxycycline or attenuated with cyclosporine A treatment

thick skin ( J:147438 )

• the epidermis is 3.2- and 3.1- fold thicker in the ear and backs, respectively, than in controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
psoriasis		DOID:8893	OMIM:PS177900	J:147438

Genotype
MGI:3815534

cx3

• Allelic Composition: Tg(KRT5-tTA)1216Glk/0; Tg(tetO-TGFB1*C223S*C225S)1Glk/0
• Genetic Background: involves: FVB/N

mortality/aging

mortality/aging ( J:70670 )

N • when pregnant mice are maintained on 10 ug/ml or higher doxycycline, double-transgenic mice with normal morphology are born at expected ratios

perinatal lethality, complete penetrance ( J:70670 )

• 1-5 ug/ml doxycycline treatment during gestation allows full-term development of double-transgenic mice, but pups are born dead or die shortly after birth

prenatal lethality, complete penetrance ( J:70670 )

• no live animals are obtained in litters born when the pregnant mouse does not receive doxycycline during gestation

growth/size/body

decreased body size ( J:70670 )

• animals born dead or dying shortly after birth with 1-5 ug/ml doxycycline treatment during gestation are runted

immune system

skin inflammation ( J:70670 )

• weanlings treated by doxycycline withdrawal displays a variable neutrophilic infiltrate characterized by microabcesses within and above cornified layers

dermatitis ( J:70670 )

• weanlings treated by doxycycline withdrawal develop dermatitis on scalp and shoulders, as well as ventral surface; dermatitis extends caudally with time

cellular

decreased cell proliferation ( J:70670 )

• cell proliferation in the epidermis is significantly reduced in double transgenic newborns after 1-5 ug/ml doxycycline treatment during gestation

integument

abnormal coat/ hair morphology ( J:70670 )

• abnormalities manifest several weeks later than in Tg(tetO-TGFB1*C223S*C225S)1Glk/Tg(KRT5-rtTA)1Glk double-transgenic mice treated with doxycycline

• with reintroduction of doxycycline at >5 ug/ml in diet, nearly complete hair regrowth is observed within 14 days

progressive hair loss ( J:70670 )

• weanlings treated by doxycycline withdrawal display progressive hair loss

abnormal hair follicle morphology ( J:70670 )

• in weanlings treated by doxycycline withdrawal, many hair follicles appear hyperplastic with abnormal morphologies

decreased hair follicle number ( J:70670 )

• hair follicle density is reduced in affected newborns after 1-5 ug/ml doxycycline treatment during gestation

abnormal skin morphology ( J:70670 )

• hyperkeratosis and other abnormalities manifest several weeks later than in Tg(tetO-TGFB1*C223S*C225S)1Glk/Tg(KRT5-rtTA)1Glk double-transgenic mice treated with doxycycline

• with reintroduction of doxycycline at >5 ug/ml in diet, hyperkeratotic phenotype is reversed

abnormal dermal layer morphology ( J:70670 )

• dermal layer in affected double-transgenic newborns is hypervascular after 1-5 ug/ml doxycycline treatment during gestation

thick dermal layer ( J:70670 )

• significant thickening is observed in weanlings treated by doxycycline withdrawal

abnormal epidermal layer morphology ( J:70670 )

• affected double-transgenic newborns after 1-5 ug/ml doxycycline treatment during gestation have reduced number of cornified layers

hyperkeratosis ( J:70670 )

• weanlings treated by doxycycline withdrawal develop hyperkeratosis

acanthosis ( J:70670 )

• epidermis of affected mice (weanlings treated by doxycycline withdrawal) becomes acanthotic

epidermal hyperplasia ( J:70670 )

• epidermis of affected mice (weanlings treated by doxycycline withdrawal) exhibits hyperplasia

thin epidermis ( J:70670 )

• epidermis is thinner in affected double-transgenic newborns than single-transgenic pups

reddish skin ( J:70670 )

• animals born dead or dying shortly after birth with 1-5 ug/ml doxycycline treatment during gestation have shiny tight erythemic skin

shiny skin ( J:70670 )

tight skin ( J:70670 )

abnormal skin physiology ( J:70670 )

• abnormalities manifest several weeks later than in Tg(tetO-TGFB1*C223S*C225S)1Glk/Tg(KRT5-rtTA)1Glk double-transgenic mice treated with doxycycline

skin inflammation ( J:70670 )

• weanlings treated by doxycycline withdrawal displays a variable neutrophilic infiltrate characterized by microabcesses within and above cornified layers

dermatitis ( J:70670 )

• weanlings treated by doxycycline withdrawal develop dermatitis on scalp and shoulders, as well as ventral surface; dermatitis extends caudally with time

Genotype
MGI:3834667

cx4

• Allelic Composition: Tg(KRT5-tTA)1216Glk/0; Tg(tetO-LMNA*G608G,-EGFP)VF1-07Maer/0
• Genetic Background: involves: FVB/N

mortality/aging

premature death ( J:145312 )

• median survival is 14 weeks for mice withdrawn from doxycycline at 21 days and 7 weeks for those withdrawn at P0

• median survival can be increased from 7 weeks to 29 by providing mice with soft pellets on the cage floor

skeleton

abnormal lower incisor morphology ( J:145312 )

• following doxycycline withdrawal at birth, mice exhibit changes in the lower incisors and surrounding tissue unlike in wild-type mice

craniofacial

abnormal mouth morphology ( J:145312 )

• following doxycycline withdrawal at birth, mice exhibit increased impaction of food or bedding material with acute inflammation to overt necrosis of the pulp, accumulation of cellulose in the pulp, and spread of inflammation into the periodontal ligament and surrounding bony structure unlike in wild-type mice

abnormal lower incisor morphology ( J:145312 )

• following doxycycline withdrawal at birth, mice exhibit changes in the lower incisors and surrounding tissue unlike in wild-type mice

digestive/alimentary system

stomach hypoplasia ( J:145312 )

• following doxycycline withdrawal, mice exhibit hypoplasia in the stomach unlike in wild-type mice

growth/size/body

abnormal mouth morphology ( J:145312 )

• following doxycycline withdrawal at birth, mice exhibit increased impaction of food or bedding material with acute inflammation to overt necrosis of the pulp, accumulation of cellulose in the pulp, and spread of inflammation into the periodontal ligament and surrounding bony structure unlike in wild-type mice

abnormal lower incisor morphology ( J:145312 )

• following doxycycline withdrawal at birth, mice exhibit changes in the lower incisors and surrounding tissue unlike in wild-type mice

decreased body weight ( J:145312 )

• at 7 weeks of age in mice withdrawn from doxycycline at birth

endocrine/exocrine glands

abnormal sebocyte differentiation ( J:145312 )

• six weeks after withdrawal of doxycycline, sebaceous glands exhibit irregular maturation of sebocytes unlike in wild-type mice

enlarged sebaceous gland ( J:145312 )

• six weeks after withdrawal of doxycycline, sebaceous glands appear enlarged and displaced

sebaceous gland hyperplasia ( J:145312 )

• six weeks after withdrawal of doxycycline, sebaceous glands exhibit hyperplasia unlike in wild-type mice

sebaceous gland hypoplasia ( J:145312 )

• 17 weeks after doxycycline withdrawal, sebaceous glands appear hypoplastic

immune system

periodontium inflammation ( J:145312 )

• following doxycycline withdrawal at birth, mice exhibit spread of inflammation into the periodontal ligament and surrounding bony structure unlike in wild-type mice

• however, no changes were seen in the upper jaws

skin inflammation ( J:145312 )

• six weeks after withdrawal of doxycycline, inflammatory cells infiltrate the dermis unlike in wild-type mice

integument

abnormal sebocyte differentiation ( J:145312 )

• six weeks after withdrawal of doxycycline, sebaceous glands exhibit irregular maturation of sebocytes unlike in wild-type mice

enlarged sebaceous gland ( J:145312 )

• six weeks after withdrawal of doxycycline, sebaceous glands appear enlarged and displaced

sebaceous gland hyperplasia ( J:145312 )

• six weeks after withdrawal of doxycycline, sebaceous glands exhibit hyperplasia unlike in wild-type mice

sebaceous gland hypoplasia ( J:145312 )

• 17 weeks after doxycycline withdrawal, sebaceous glands appear hypoplastic

skin inflammation ( J:145312 )

• six weeks after withdrawal of doxycycline, inflammatory cells infiltrate the dermis unlike in wild-type mice

sparse hair ( J:145312 )

• following doxycycline withdrawal, mice have thin coats

• however, hair follicle number is normal

abnormal hypodermis morphology ( J:145312 )

• absent 17 weeks after withdrawal of doxycycline

abnormal hair follicle morphology ( J:145312 )

• six weeks after withdrawal of doxycycline

abnormal dermal layer morphology ( J:145312 )

• six weeks after withdrawal of doxycycline, inflammatory cells infiltrate the dermis unlike in wild-type mice

• 17 weeks after doxycycline withdrawal, the dermis exhibits fibrosis unlike in wild-type mice

hyperkeratosis ( J:145312 )

• six weeks after withdrawal of doxycycline

abnormal epidermis stratum granulosum morphology ( J:145312 )

• six weeks after withdrawal of doxycycline, mice exhibit hypergranulosis unlike wild-type mice

epidermal hyperplasia ( J:145312 )

• six weeks after withdrawal of doxycycline, mice exhibit slight to moderate hyperplasia of the interfollicular epidermis unlike in wild-type mice

• after withdrawal of doxycycline, some areas exhibit severe hyperplasia unlike in wild-type mice

skin lesions ( J:145312 )

• six weeks after withdrawal of doxycycline, mice exhibit skin lesions of varying severity unlike in wild-type mice

skin fibrosis ( J:145312 )

• 17 weeks after doxycycline withdrawal, the dermis exhibits fibrosis unlike in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
progeria		DOID:3911	OMIM:176670	J:145312

Genotype
MGI:3834668

cx5

• Allelic Composition: Tg(KRT5-tTA)1216Glk/0; Tg(tetO-LMNA,-EGFP)SF1-04Maer/0
• Genetic Background: involves: FVB/N

integument

integument phenotype ( J:145312 )

N • skin morphology is normal following doxycycline withdrawal