Mouse Genome Informatics
cn1
    Macf1tm1Efu/Macf1tm1Efu
Tg(KRT14-cre)1Efu/0

involves: 129
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• areas of hyperproliferating epithelium at wound sites are decreased by more than 30% over 2 to 4 days after injury compared to in similarly treated wild-type mice
• during an in vitro wound healing assay, keratinocyte move only 20% of the distance into the gap unlike wild-type cells

integument
• during an in vitro wound healing assay, keratinocyte move only 20% of the distance into the gap unlike wild-type cells
• keratinocytes, in culture, exhibit a 60% decrease in average migration speed on fibronectin compared to wild-type cells
• however, rates of proliferation and apoptosis are normal, and reducing the underlying matrix protein in culture can restore migration speeds to normal
• keratinocytes exhibit stronger focal adhesions in culture than wild-type cells


Mouse Genome Informatics
cn2
    Dsptm1Efu/Dsptm1Efu
Tg(KRT14-cre)1Efu/0

involves: 129/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• mice have severe intracellular adhesion defects

integument
• large sections of the epidermis are missing and visible peeling occurs (J:67797)
• after mechanical stress, newborn mice show epithelial peeling (J:73084)
• at E18.5, intracellular separation is pronounced
• cornified envelopes are bubble-bath like
• at E18.5, intracellular separation is pronounced


Mouse Genome Informatics
cn3
    Tcf3tm1.1Efu/Tcf3tm1.1Efu
Tg(KRT14-cre)1Efu/0

involves: 129/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• mice appear phenotypically normal


Mouse Genome Informatics
cn4
    Tcf3tm1.1Efu/Tcf3tm1.1Efu
Tcf7l2tm1Cle/Tcf7l2tm1Cle
Tg(KRT14-cre)1Efu/0

involves: 129/Sv * 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• hair follicles appear but exhibit defects in subsequent down-growth compared to in wild-type mice
• in skin grafts
• newborn mice often lack whiskers unlike wild-type mice
• basal cells are flattened unlike in wild-type mice
• in newborn mice
• at P0, skin cells exhibit increased cell death compared to in wild-type mice
• grafted skin exhibits no hair and shrunk area without inflammation compared with wild-type skin grafts
• cultured skin epithelial fails to undergo long-term tissue maintenance unlike wild-type skin
• cultured keratinocytes from P0 mice exhibit decreased proliferation compared with wild-type cells

cellular
• cultured keratinocytes from P0 mice exhibit decreased proliferation compared with wild-type cells


Mouse Genome Informatics
cn5
    Map2k1tm1Chrn/Map2k1tm1Chrn
Map2k2tm1Chrn/Map2k2tm1Chrn
Tg(KRT14-cre)1Efu/?

involves: 129/Sv * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• the majority of mice die within 24 hours of birth

digestive/alimentary system
• mice display full-thickness epithelium death and detachment from the underlying tissue
• however, suckling behavior was not altered

growth/size/body
• mice display full-thickness epithelium death and detachment from the underlying tissue
• however, suckling behavior was not altered
• ear flaps are detached
• mice are smaller at birth
• mice lose 4%-10% of birth weight within 6 hours

hearing/vestibular/ear
• ear flaps are detached

vision/eye
• in some mice

homeostasis/metabolism
• mice lose 4%-10% of birth weight within 6 hours and dye is more readily absorbed than in wild-type mice

craniofacial
• mice display full-thickness epithelium death and detachment from the underlying tissue
• however, suckling behavior was not altered
• ear flaps are detached

integument
• at E17.5, keratinocytes in the basal layer but not in the hair follicles undergo increased apoptosis compared to normal
• mice lose 4%-10% of birth weight within 6 hours and dye is more readily absorbed than in wild-type mice
• fewer hair follicles are present including 37% fewer peleage follicles
• hair follicles undergo reduced proliferation
• 90% fewer vibrissae follicles compared to wild-type mice
• epidermis is hypoplastic

cellular
• at E17.5, keratinocytes in the basal layer but not in the hair follicles undergo increased apoptosis compared to normal


Mouse Genome Informatics
cn6
    Ctnnb1tm4Wbm/Ctnnb1tm4Wbm
Tg(KRT14-cre)1Efu/0

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die shortly after birth

integument
• in newborns and when skin is grafted onto wild-type mice


Mouse Genome Informatics
cn7
    Ezh1tm1Jnw/Ezh1tm1Jnw
Ezh2tm1Tara/Ezh2tm1Tara
Tg(KRT14-cre)1Efu/0

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die within 24 hours of birth

integument
N
• mice do not exhibit skin inflammation (J:169295)
• hair follicles in skin grafts arrest in the first growth phase of the hair cycle
• skin grafts on nude mice remain hairless unlike wild-type grafts
• skin grafts exhibit hyperproliferation in the infundibulum compared with wild-type cells
• hair follicle stem cells in the lower outer root sheath zone exhibit decreased proliferation compared with wild-type cells
• hair follicle stem cells in the lower outer root sheath zone exhibit decreased proliferation regardless of stimulation compared with wild-type cells
• hair follicle cells exhibit increased apoptosis unlike wild-type cells
• hair follicles in skin grafts arrest in the first growth phase of the hair cycle

behavior/neurological


Mouse Genome Informatics
cn8
    Ago2tm1.1Tara/Ago2tm1.1Tara
Tg(KRT14-cre)1Efu/0

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• no developmental defects are detected


Mouse Genome Informatics
cn9
    Ago1tm1.1Tara/Ago1tm1.1Tara
Ago2tm1.1Tara/Ago2tm1.1Tara
Tg(KRT14-cre)1Efu/0

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• evaginating hair follicle cysts in the epidermis at P4
• shortened and misangled hair follicle growth at P4
• hyperthickened
• evaginating hair follicle cysts in the epidermis at P4
• apoptotic cells in the basal epidermis


Mouse Genome Informatics
cn10
    Dicer1tm1Tara/Dicer1tm1Tara
Tg(KRT14-cre)1Efu/0

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• less developed hair coat at P4.5
• evaginating hair follicle cysts in the epidermis at P4
• shortened and misangled hair follicle growth at P4 (J:183622)
• mice exhibit the loss of hair follicle stem cells in the bulge unlike in wild-type cells (J:201587)
• dehydrated at P4.5
• evaginating hair follicle cysts in the epidermis at P4
• apoptotic cells in the basal epidermis

growth/size/body


Mouse Genome Informatics
cn11
    Ctnnb1tm4Wbm/Ctnnb1+
Tg(KRT14-cre)1Efu/0

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Lack of hair follicles in Ctnnb1tm4Wbm/Ctnnb1+ Tg(KRT14-cre)1Efu/0 mice

integument


Mouse Genome Informatics
cn12
    Dicer1tm1Tara/Dicer1tm1Tara
Tg(KRT14-cre)1Efu/?

involves: 129P2/OlaHsd * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• began to lose weight within 1-2 day after birth, and died by day 6
• mutant mice are normal at birth and continued to feed for several days

homeostasis/metabolism
• appeared dehydrated before death

cellular
• showed signs of apoptosis in skin as early as E17.5
• frequency of apoptosis was higher in the hair germ
• at P6.5, apoptosis is enriched in hair follicles, including abnormal cysts in the epidermis

integument
• hair germs appear to evaginate into the epidermis
• hair germ-like cysts became prevalent, markedly distorting the overlying epidermis
• showed malformed whiskers


Mouse Genome Informatics
cn13
    Cdh1tm2Kem/Cdh1tm2Kem
Tg(KRT14-cre)1Efu/0
Tg(Krt14-RNAi:Cdh3)1Efu/0

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die within 1 to 2 hours of birth

growth/size/body
• mice are small at birth

homeostasis/metabolism
• unlike in wild-type mice, dye is readily absorbed through the paws, facial skin, ear buds and lower belly

integument
• mice exhibit focal gaps in the epithelial sheets of the epidermis due to degeneration of cells
• however, desmosomes are still present in normal numbers
• intercellular junctions are perturbed unlike in wild-type epidermis
• adherence and tight junction components fail to localize to cell borders unlike in wild-type epidermis
• the typically columnar orientation of cells within the basal layer and flattened squamous morphology of the suprabasal cells are lost
• cells in the spinous layer fail to flatten as in wild-type mice
• the typically columnar orientation of cells within the basal layer and flattened squamous morphology of the suprabasal cells are lost
• unlike in wild-type mice, cells within condensed nuclei indicating apoptosis are found in the suprabasal layer
• suprabasal keratin intermediate filament organization is perturbed compared to in wild-type mice
• around the mouth, umbilicus and tail
• ventrally
• skin is inflexible
• mice exhibit increased apoptosis in the epidermis compared to wild-type mice
• however, cell proliferation in the epidermis is normal, and no inflammatory response is observed
• unlike in wild-type mice, dye is readily absorbed through the paws, facial skin, ear buds and lower belly


Mouse Genome Informatics
cn14
    Kdrtm1.1Jamb/Kdrtm1.1Jamb
Tg(KRT14-cre)1Efu/0

involves: 129S1/Sv * 129X1/SvJ * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• skin lymphatic vessels are dilated and hyperplastic compared to in wild-type mice


Mouse Genome Informatics
cn15
    Porcntm1.1Vdv/Y
Tg(KRT14-cre)1Efu/0

involves: 129S4/SvJaeSor * 129S5/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Dental and skin abnormalities and alopecia in Porcntm1.1Vdv/Y Tg(KRT14-cre)1Efu/0 mice

integument
• in areas with thin skin the subcutaneous fat is directly adjacent to the outermost epidermal layers (J:186934)
• have large areas of thin skin with alopecia (J:186934)
• mosaic pattern of the phenotype is consistent with variable Cre expression (J:186934)
• early budding of epidermal cells to form the hair placodes does not take place (J:186934)
• have large areas of thin skin with alopecia (J:186934)
• mosaic pattern of the phenotype is consistent with variable Cre expression (J:186934)

craniofacial
• missing and hypoplastic teeth (J:186934)

adipose tissue
• in areas with thin skin the subcutaneous fat is directly adjacent to the outermost epidermal layers (J:186934)

growth/size/body
• missing and hypoplastic teeth (J:186934)

Mouse Models of Human Disease
OMIM IDRef(s)
Focal Dermal Hypoplasia; FDH 305600 J:186934


Mouse Genome Informatics
cn16
    Porcntm1.1Vdv/Porcn+
Tg(KRT14-cre)1Efu/0

involves: 129S4/SvJaeSor * 129S5/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• barely detectable hair loss (J:186934)


Mouse Genome Informatics
cn17
    Itgb1tm1Efu/Itgb1tm1Efu
Tg(KRT14-cre)1Efu/0

involves: 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• usually die within a few hours of birth

integument
• hair follicle keratinocytes fail to remodel basement membrane and invaginate into the dermis
• developing hair follicles are scarce, although a few mature hair follicles, most likely guard hairs, are detected
• epidermal proliferation is inhibited, however a spatial and temporal program of terminal differentiation does occur
• basal cells of the epidermis are flat and the nucleus is oriented parallel to the basement membrane
• epidermis consists of a flattened basal layer and only one or two layers of suprabasal layers before the stratum corneum
• many areas of skin exhibit separations at the dermal-epidermal junction, such that in severely affected areas, the epidermis is detached entirely from the dermis
• severe skin blistering
• exhibit separation of the dermal-epidermal junction upon mechanical trauma, indicating fragile skin, however do not display denuding
• thin and fragile

cellular
• basement membrane assembly/organization is impaired, leading to a loss of extracellular matrix and hemidesmosomes
• skin shows discontinuity of the lamina densa


Mouse Genome Informatics
cn18
    Ctnna1tm1Efu/Ctnna1tm1Efu
Tg(KRT14-cre)1Efu/?

involves: 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• mice have severe intracellular adhesion defects
• in culture, keratinocytes overgrow the monolayer, grow faster than wild-type cells, do not require a feeder layer, are more sensitive to growth factors, and have an increased ability to breakdown matrix

craniofacial

limbs/digits/tail
• limbs fail to develop completely

integument
• in culture, keratinocytes overgrow the monolayer, grow faster than wild-type cells, do not require a feeder layer, are more sensitive to growth factors, and have an increased ability to breakdown matrix
• mice have diminished signs of hair follicle development
• epidermal-dermal boundary was difficult to discern
• clumps of keratinocytes with morphology and differentiation characteristic of epidermis and not hair follicles and that are devoid of surface epidermis are present within the dermis
• large sections of the epidermis are missing
• epidermis is thick and disorganized, particularly within the basal cell layer
• basal cells are round and spinous
• keratinocytes are frequently binucleated and unusually large
• visible peeling occurs
• epidermis is thick and disorganized, particularly within the basal cell layer
• epidermal-dermal boundary was difficult to discern

growth/size/body


Mouse Genome Informatics
cn19
    Atf2tm3Nicj/Atf2tm3Nicj
Tg(KRT14-cre)1Efu/?

involves: C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• the median appearance of skin papillomas after topical application of carcinogens is five to six weeks earlier than in littermate controls
• mice have significantly greater numbers of papillomas 20 weeks after carcinogen treatment with a mean of 7 compared to 3 in littermate controls

integument
• the percentage of proliferating epithelial cells after TPA administration is twice that of littermate controls
• reduced levels of active caspase 3 were observed in the skin of mice treated with carcinogens suggesting apoptosis levels might be lower
• mice develop a significantly thickened hyperdermis after three topical applications of TPA
• thickness is twice that of wild-type mice after TPA application
• the median appearance of skin papillomas after topical application of carcinogens is five to six weeks earlier than in littermate controls
• mice have significantly greater numbers of papillomas 20 weeks after carcinogen treatment with a mean of 7 compared to 3 in littermate controls


Mouse Genome Informatics
cn20
    Casp8tm1Hed/Casp8tm1Hed
Tg(KRT14-cre)1Efu/0

Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• about 90% of mutants die by P15, while 10% survive for months
• about 10% of mutants exhibit a mosaic skin phenotype and survive for months

integument
• mutants exhibit an increase in epidermal water loss
• mutants develop atopic dermatitis-like skin disease
• about 90% of mutants exhibit a uniform skin phenotype and die by P15 while mutants that survive longer than P15, exhibit the skin phenotype on the posterior region of the back skin
• 2.5-fold increase in the numbers of blood vessels in the skin as indicated by marker analysis
• cutaneous edema is seen in the ears and feet
• affected skin of mutants surviving longer than P15 shows suprabasal cells with increased intracellular space, indicating development of spongiosis
• hyperproliferation of epithelial stem/progenitor cells in the skin
• the intracellular adhesion apparatus of the epidermis is disrupted, with keratinocytes showing an abnormal punctate localization of E-cadherin (Cdh1) due to increased shedding of E-cadherin
• mutants exhibit epidermal hyperplasia
• topical application of clobetasol, a corticosteroid, substantially reduces the epidermal hyperplasia and abolishes the epidermal gaps

immune system
• mutants exhibit an increase in mast cells with age
• IgE levels are normal in young mutants but adults show a 30-fold increase compared to wild-type mice
• 5-fold increase in serum IgG1 levels in adults
• marker analysis indicates that mutants exhibit a biphastic T-helper cell response, with a TH2 response during the acute phase of dermatitis followed by a TH1 response during the chronic phase of dermatitis
• mutants develop atopic dermatitis-like skin disease
• about 90% of mutants exhibit a uniform skin phenotype and die by P15 while mutants that survive longer than P15, exhibit the skin phenotype on the posterior region of the back skin

homeostasis/metabolism
• cutaneous edema is seen in the ears and feet
• affected skin of mutants surviving longer than P15 shows suprabasal cells with increased intracellular space, indicating development of spongiosis
• mutants exhibit an increase in epidermal water loss

hematopoietic system
• mutants exhibit an increase in mast cells with age
• IgE levels are normal in young mutants but adults show a 30-fold increase compared to wild-type mice
• 5-fold increase in serum IgG1 levels in adults
• marker analysis indicates that mutants exhibit a biphastic T-helper cell response, with a TH2 response during the acute phase of dermatitis followed by a TH1 response during the chronic phase of dermatitis

cardiovascular system
• 2.5-fold increase in the numbers of blood vessels in the skin as indicated by marker analysis

Mouse Models of Human Disease
OMIM IDRef(s)
Dermatitis, Atopic 603165 J:167299


Mouse Genome Informatics
cn21
    Ago1tm1.1Tara/Ago1tm1.1Tara
Tg(KRT14-cre)1Efu/0

Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• no developmental defects are detected


Mouse Genome Informatics
cx22
    Ctnnd1tm1Abre/Ctnnd1tm1Abre
Tg(KRT14-cre)1Efu/?

involves: 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mice die of an inflammatory skin disease by day 15 so to study effects of the alleles on skin cancer, new born back skin was grafted onto immunocompromised nude mice
• within 15 to 50 days after engraftment, 100% of grafts display signs of epidermal hyperkeratosis compared with their wild-type counterparts
• 50 days after engraftment, grafts develop raised nodules that soon began to ulcerate and adopt an erythematous crateriform appearance
• epithelial undulations with eosinophilic keratinized debris accompany the papilloma-like protuberances 50 days post engraftment
• by 70 days, dysplastic keratinocytes had populated the invaginations
• aberrant clusters of pigment-filled melanocytes, typically confined to skin epithelium, are frequent in the dermis after 70 days

cellular
• binucleated cells are observed in newborn skin that is grafted onto nude mice
• these cells are often observed in differentiating layers

integument
• new born back skin grafted onto immunocompromised nude mice have a paucity of hair due to the development of skin tumors
• there is an enhancement of actively cycling cells in new born back skin grafted onto immunocompromised nude mice
• this hyperproliferation is dependent on surrounding inflammation and will normalize under anti-inflammatory treatment
• mice die of an inflammatory skin disease by day 15 so to study effects of the alleles on skin cancer, new born back skin was grafted onto immunocompromised nude mice
• within 15 to 50 days after engraftment, 100% of grafts display signs of epidermal hyperkeratosis compared with their wild-type counterparts
• 50 days after engraftment, grafts develop raised nodules that soon began to ulcerate and adopt an erythematous crateriform appearance
• epithelial undulations with eosinophilic keratinized debris accompany the papilloma-like protuberances 50 days post engraftment
• by 70 days, dysplastic keratinocytes had populated the invaginations
• aberrant clusters of pigment-filled melanocytes, typically confined to skin epithelium, are frequent in the dermis after 70 days