Analysis Tools|
Allele Symbol Allele Name Allele ID |
Tg(KRT5-cre)5132Jlj transgene insertion 5132, Jose Luis Jorcano MGI:3050065 |
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| Summary |
40 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Background Sensitivity: compared to on a congenic FVB background, mice exhibit later lethality
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• Background Sensitivity: compared to on a congenic FVB background, mice exhibit less skin thickening
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• majority of auchene hair type are altered in shape, many with more pronounced bends
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• adult coat appears less dense and ruffled than controls
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• about 90% of zigzag (ZZ) type hair show much less pronounced bends in 6-month old adults
• hair forms exhibit a variable number of bends compared to the three bend in control hairs; many do not have alternating bend patterns of control hairs, but have 2 bends in same direction
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• ~90% of zigzag (ZZ) type hair shows much less pronounced bends in 6-month old adults
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• majority of auchene hair type are altered in shape, many with more pronounced bends
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• adult coat appears less dense and ruffled than controls
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• about 90% of zigzag (ZZ) type hair show much less pronounced bends in 6-month old adults
• hair forms exhibit a variable number of bends compared to the three bend in control hairs; many do not have alternating bend patterns of control hairs, but have 2 bends in same direction
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• ~90% of zigzag (ZZ) type hair shows much less pronounced bends in 6-month old adults
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Background Sensitivity: compared to on a congenic C57BL/6 background, mice exhibit earlier lethality
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• Background Sensitivity: compared to on a congenic C57BL/6 background, mice exhibit more skin thickening
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most mice die but some survive
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• most mice die but some survive
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• mice exhibit eye defects
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• mice exhibit hair defects
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• slightly
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal footpad pigmentation and normal Kitl mRNA levels in the footpad epidermis at P30, indicating complete reversal of the phenotype observed in mice that are only heterozygous for Rps6tm1Gtho and hemizygous for Tg(KRT5-cre)5132Jlj
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit an intermediate footpad pigmentation phenotype and reduced Kitl mRNA levels in the footpad epidermis at P30, indicating partial amelioration of the dark skin observed in mice that are only heterozygous for Rps6tm1Gtho and hemizygous for Tg(KRT5-cre)5132Jlj
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• mice exhibit an intermediate footpad pigmentation phenotype and reduced Kitl mRNA levels in the footpad epidermis at P30, indicating partial amelioration of the dark skin observed in mice that are only heterozygous for Rps6tm1Gtho and hemizygous for Tg(KRT5-cre)5132Jlj
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• mice exhibit an intermediate footpad pigmentation phenotype and reduced Kitl mRNA levels in the footpad epidermis at P30, indicating partial amelioration of the dark skin observed in mice that are only heterozygous for Rps6tm1Gtho and hemizygous for Tg(KRT5-cre)5132Jlj
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increase in transepidermal water loss, indicating an epidermal barrier defect
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• increase in transepidermal water loss, indicating an epidermal barrier defect
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• all females are sterile
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• most males are sterile
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• inflammation occurs frequently around 3 to 4 months of age at the ears and around the eyes
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• inflammation occurs frequently around 3 to 4 months of age at the ears and around the eyes
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• microblisters occur at the dermis-epidermis junction
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• epidermis is thickened around the ears, the eyes, and at sites of microblistering
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die between E16 and E18.5
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• mice exhibit severely reduced dermal lymphatic capilliaries compared with control mice
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• severe
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die between E16 and E18.5
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• lymphatic vessel networks are less interconnected than in control mice
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• fine vessels are absent
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• severe
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit markedly darkened ears relative to control mice
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• mice exhibit markedly darkened hair relative to control mice
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• mice show increased epidermal pigmentation in the footpads, tail and ears
• skin is much darker than that observed in single Rps19Mhdadsk3 or Rps20Mhdadsk4 heterozygotes
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• mice exhibit markedly darkened footpads relative to control mice
• Kitl (kit ligand) mRNA levels are increased 8.2- and 3.8-fold at P3 and P30, respectively, in the footpad epidermis relative to control mice
• i.p. injection of ACK2 (a Kit-neutralizing antibody) at P2 prevents the appearance of dark footpads at P8 whereas PBS injection has no effect on pigmentation, indicating that Kit signaling is required for dark skin
• at P30, a 73-fold increase in Trp53 staining is noted in the basal layer of the footpad epidermis relative to control mice
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• mice exhibit markedly darkened tails relative to control mice
• pigment accumulates in the tail epidermis, whereas the dermis is unaffected
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• mice exhibit markedly darkened ears relative to control mice
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• mice exhibit markedly darkened hair relative to control mice
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• mice show increased epidermal pigmentation in the footpads, tail and ears
• skin is much darker than that observed in single Rps19Mhdadsk3 or Rps20Mhdadsk4 heterozygotes
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• mice exhibit markedly darkened footpads relative to control mice
• Kitl (kit ligand) mRNA levels are increased 8.2- and 3.8-fold at P3 and P30, respectively, in the footpad epidermis relative to control mice
• i.p. injection of ACK2 (a Kit-neutralizing antibody) at P2 prevents the appearance of dark footpads at P8 whereas PBS injection has no effect on pigmentation, indicating that Kit signaling is required for dark skin
• at P30, a 73-fold increase in Trp53 staining is noted in the basal layer of the footpad epidermis relative to control mice
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• mice exhibit markedly darkened tails relative to control mice
• pigment accumulates in the tail epidermis, whereas the dermis is unaffected
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• mice exhibit markedly darkened footpads relative to control mice
• Kitl (kit ligand) mRNA levels are increased 8.2- and 3.8-fold at P3 and P30, respectively, in the footpad epidermis relative to control mice
• i.p. injection of ACK2 (a Kit-neutralizing antibody) at P2 prevents the appearance of dark footpads at P8 whereas PBS injection has no effect on pigmentation, indicating that Kit signaling is required for dark skin
• at P30, a 73-fold increase in Trp53 staining is noted in the basal layer of the footpad epidermis relative to control mice
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• mice exhibit markedly darkened tails relative to control mice
• pigment accumulates in the tail epidermis, whereas the dermis is unaffected
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• mice exhibit markedly darkened ears relative to control mice
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• mice exhibit markedly darkened ears relative to control mice
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• mice exhibit markedly darkened ears relative to control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• DMBA and TPA treated mice develop papillomas within 8 weeks compared to 3 months in mice treated with TPA alone or 34 weeks in similarly treated wild-type mice
• mice treated with DMBA develop squamous cell carcinomas from existing papillomas
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• in 10% of mice older than 8 months, hyperthickened and keratinized papillomas form in regions of mechanical stress unlike in wild-type mice
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• unlike in wild-type mice, macrophages infiltrate into the adipose tissue
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• 38% increase in the epidermis
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• unlike in wild-type mice, macrophages infiltrate into the dermis
• the number of gamma-delta T cells is increased 38% in the epidermis compared to in wild-type mice
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• DMBA and TPA treated mice develop papillomas within 8 weeks compared to 3 months in mice treated with TPA alone or 34 weeks in similarly treated wild-type mice
• mice treated with DMBA develop squamous cell carcinomas from existing papillomas
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• 38% increase in the epidermis
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• unlike in wild-type mice, macrophages infiltrate into the adipose tissue
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• in the tails of older mice and nipples of younger virgin females
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• after P6, sebaceous glands atrophy and are absent by 3 months
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• unlike in wild-type mice, macrophages infiltrate into the dermis
• the number of gamma-delta T cells is increased 38% in the epidermis compared to in wild-type mice
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• disorganized structure and thin
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• long claws
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• disorganized structure
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• at P16, many follicles extend down beneath the dermis with some reaching to the muscle layer at the base of the adipose tissue unlike in wild-type mice
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• the first wave of hair follicle cycling is asynchronous unlike in wild-type mice
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• in the nipples of younger virgin females
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• in 10% of mice older than 8 months, hyperthickened and keratinized papillomas form in regions of mechanical stress unlike in wild-type mice
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• after P6, sebaceous glands atrophy and are absent by 3 months
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• in the tails of older mice and nipples of younger virgin females
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• in the nipples of younger virgin females
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice with a maternally inherited cre transgene die before weaning
• however, mice with a paternally inherited cre transgene are viable
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• mice with a paternally inherited cre transgene develop tumors following chronic exposure to 125 J/m2 UVB unlike control mice
• tumors appear earlier and grow faster in mice with a paternally inherited cre transgene compared to control mice receiving a 16-fold higher dose of UVB
• the cumulative UVB EC50 for tumor development is 3.75 kJ/m2 in mice with a paternally inherited cre transgene compared to 140 kJ/m2control mice
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• mice with a maternally inherited cre transgene are severely runted at birth
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• mice with a maternally inherited cre transgene develop premature polyploidy in hepatocytes
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• the minimal erythemal dose of UVB is 40 J/m2 in mice with a paternally inherited cre transgene compared to 900 J/m2 in controls
• in mice with a paternally inherited cre transgene sensitivity to UVB induced changes in the epidermis (hyperplasia, hypertrophy, hypergranulosis, and hyperkeratosis) are increased
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die slightly earlier than Chuktm1Yhu/Chuktm1Yhu Tg(KRT5-cre)1Jlj mice
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• as in Chuktm1Yhu/Chuktm1Yhu Tg(KRT5-cre)1Jlj mice
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• as in Chuktm1Yhu/Chuktm1Yhu Tg(KRT5-cre)1Jlj mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most mice die between 12 and 16 days after birth and all are dead by day 22
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• the esophagus is small
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• at birth, mice resemble Chuktm1Mka homozygotes
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• mice exhibit increased keratinocyte cell numbers compared to in wild-type mice
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• at birth, mice resemble Chuktm1Mka homozygotes
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• hyperproliferative keratinocytes do not terminally differentiate
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• mice exhibit epidermal hyperproliferation that is keratinocyte autonomous
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• beginning at P5 and gradually increasing through lifespan
• however, treatment with GW2974, an EGFR and ErbB2 inhibitor, can reduce epidermal thickening
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• 5 days after birth
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• 5 days after birth
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• hyperproliferative keratinocytes do not terminally differentiate
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• mice exhibit increased keratinocyte cell numbers compared to in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal epidermal thickness
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• epidermal proliferation is less than in Chuktm1Yhu/Chuktm1Yhu Tg(KRT5-cre)1Jlj mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Absence of vascular defects in the skin of adult Igs1tm11(CAG-Bgeo,-Edn2)Nat/Igs1+ Tg(KRT5-cre)5132Jlj/0 mice
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• massive increase in dermal pigmentation
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• massive increase in dermal pigmentation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice are fertile
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• enlarged with age
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• accumulation of melanin in the dermis and subcutis of adults
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• enlarged with age
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• progressive hair loss beginning 1 week after birth with no regrowth of hair detected through 24 months of age; however, a few evenly spaced, frail hairs remain
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• at P14 hair shafts are often misshapen with abnormal pigmentation patterns or absent
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• most nonpermanent regions of the hair follicle are lost and no regrowth of anagen hair follicles is seen in adults
• by P14 loss of differentiation specific markers and infiltration of phagocytic cells into the lower part of the hair follicle are seen
• at P9 many hair follicles with constrictions, kinks, or diffuse thickening of the hair bulb region are seen; however at P3 hair follicles appear similar to wild-type
• by P14 almost all hair follicles are abnormal with a wider lower portion and frequently no clear hair bulb
• at P14 the outer root sheath is disrupted and abnormal, large cells are seen within the hair follicle
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• accumulation of melanin in the dermis and subcutis of adults
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• localized areas of mild fibrosis in adults; however, the epidermis is largely unaffected with normal appearing adherens junctions and basement membranes, and no blister formation
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• more severe epidermal hyperthickening is seen in response to exposure to 4-hydroxy-tamoxifen in acetone; however this response is transient disappearing about 2 weeks after cessation of treatment
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• primary keratinocytes show a severe spreading defect
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Hair and skin phenotypes of various keratinocyte conditional Itgb1 alleles
| N |
• mice are fertile unlike conditional null mice homozygous for Itgb1tm1Ref and hemizygous for Tg(KRT1-5-cre)5132Jlj
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• dermal fibrosis is accompanied by scattered melanin deposits
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• when cultured on a surface coated with collagen I and fibronectin, keratinocytes from 2.5 month old mice adhere but fail to spread and proliferate
• however, keratinocyte proliferation is similar to wild-type when cells are isolated from 6.5 month old mice
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• mildly affected
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• at P14, abnormally shaped hair follicles fail to grow as deeply into the subcutis compared to in control mice
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• loss of hair occurs between 6 and 12 months of age
• hair loss is delayed compared to conditional null mice homozygous for Itgb1tm1Ref and hemizygous for Tg(KRT1-5-cre)5132Jlj
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• coat is slightly thinner at 2 weeks of age compared to controls
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• at P14 about 60% of hair follicles are misshapen and arrested in morphogenesis
(J:148885)
• at P14 about 40% of hair follicles reach down to the muscle layer
(J:148885)
• at P14
(J:177979)
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• at P14 about 40% have severely abnormal and multilayered outer root sheaths
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• progressive hair loss is accompanied by development of dermal fibrosis with scattered melanin deposits
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• at P14 occasional small microblisters are seen at the dermal-epidermal junction
• however by 6.5 months of age almost no microblisters are seen in the epidermis of the back skin
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• dermal fibrosis is accompanied by scattered melanin deposits
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• when cultured on a surface coated with collagen I and fibronectin, keratinocytes from 2.5 month old mice adhere but fail to spread and proliferate
• however, keratinocyte proliferation is similar to wild-type when cells are isolated from 6.5 month old mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Hair and skin phenotypes of various keratinocyte conditional Itgb1 alleles
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• 70% of mice die by 6 weeks
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• mice develop an abnormal gait and walk with extended legs
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• ears become crumpled in appearance and are closely apposed to the head
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• ears become crumpled in appearance and are closely apposed to the head
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• the stratified epithelia of the esophagus displays abnormal basal cell morphology and reduced proliferation compared to in wild-type mice
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• by 7 weeks of age
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• ears become crumpled in appearance and are closely apposed to the head
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• ears become crumpled in appearance and are closely apposed to the head
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• after 4 weeks mice were 10 to 11 g compared to 20 g for wild-type mice
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• in a barrier function test, dye penetrate the superficial but not lower layers of the skin unlike in wild-type mice that demonstrate only occasional staining of the stratum corneum
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• mice develop skin inflammation with an increase in the number of macrophages around some but not all deformed hair follicles and giant cells found close to some hair bulbs
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• fibrosis is accompanied by large melanin deposits
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• at day 2, pigmentation on back skin at the midline and in several lines parallel to the ribs is reduced
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• ears become crumpled in appearance and are closely apposed to the head
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• ears become crumpled in appearance and are closely apposed to the head
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• by 7 weeks of age
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• in a barrier function test, dye penetrate the superficial but not lower layers of the skin unlike in wild-type mice that demonstrate only occasional staining of the stratum corneum
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• mice develop skin inflammation with an increase in the number of macrophages around some but not all deformed hair follicles and giant cells found close to some hair bulbs
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• at P14, abnormally shaped hair follicles fail to grow as deeply into the subcutis compared to in control mice
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• at 9 days a reduction in the number of hair follicles is apparent and by 4 weeks of age mice have few hairs left
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• loss of hair occurs between 2 and 5 weeks of age
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• short hairs are absent
(J:65038)
• beginning at day 9, hair follicles display abnormal morphologies such as shortened hair bulb and increased number of layers of outer root sheath cells, folding of layers of inner root sheath cells and amorphous, mislocated hair follicles
(J:65038)
• all hair follicles are severely distorted
(J:148885)
• at P14
(J:177979)
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• at 9 days a reduction in the number of hair follicles is apparent and by 4 weeks of age mice have few hairs left
(J:65038)
• no hair follicles are apparent at 7 weeks of age
(J:65038)
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• proliferation of hair follicles is decreased compared to in wild-type mice with proliferation of hair follicles reduced or absent at day 9 and 16, respectively
• however, there is no increase in apoptosis rates of hair follicles
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• mice develop dermal fibrosis
(J:65038)
• dermal fibrosis is detected by 5 weeks of age
(J:148885)
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• cell cycling in the basal layer is reduced compared to in wild-type mice
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• the basal keratinocyte layer is composed of several layers of roundish or polygonal cells unlike in wild-type mice
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• interfollicular epidermis consists of 2 to 7 layers of roundish, polygonal, or flattened keratinocytes that are often detached from the dermis forming large blisters
• at 5 weeks of age the epidermis of the back skin is severely hyperthickened but has fewer blisters compared to mice at 2 weeks of age
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• hyperthickened at 14 days of age
(J:177979)
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• the basement membrane at the dermal-epidermal junction is distorted compared to in wild-type mice
(J:65038)
• interfollicular epidermis consists of 2 to 7 layers of roundish, polygonal, or flattened keratinocytes that are often detached from the dermis forming large blisters
(J:148885)
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• mice develop small blisters on the tongue and esophagus at 6 weeks and blisters, bleeding and ulcerations in the anus region
(J:65038)
• interfollicular epidermis consists of 2 to 7 layers of roundish, polygonal, or flattened keratinocytes that are often detached from the dermis forming large blisters
(J:148885)
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• small skin wounds are apparent especially in areas of mechanical stress such as knees, elbows and ears
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• fibrosis is accompanied by large melanin deposits
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Hair and skin phenotypes of various keratinocyte conditional Itgb1 alleles
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• keratinocytes exhibit impaired adhesion to a collagen/fibronectin coated plastic dishes compared with control cells
(J:177979)
• keratinocytes do not adhere
(J:203018)
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• keratinocytes exhibit impaired adhesion to a collagen/fibronectin coated plastic dishes compared with control cells
(J:177979)
• keratinocytes do not adhere
(J:203018)
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• at P14, abnormally shaped hair follicles fail to grow as deeply into the subcutis compared to in control mice
|
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• at 14 days of age
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• at 2 weeks, hair coat development is impaired compared with control mice
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• hyperthickened with aberrant shaped cells at 14 days of age
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• at the epidermal-dermal junction at 14 days of age
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• at 5 weeks due to mechanical stress
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• at 2 weeks, skin pigmentation is impaired compared with control mice
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• at 2 weeks, skin pigmentation is impaired compared with control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• defective adhesion and more pronounced spreading
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• cells do not grow into a confluent monolayer and undergo rapidly initiated terminal differentiation
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• patchy hair loss over the dorsal midline of the skull
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• intermixed with normal follicles
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• less affected than in Itgb1tm1Ref/Itgb1tm1Ref Tg(KRT1-5-cre)5132Jlj mice
• however, no subepidermal blistering is observed
|
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• defective adhesion and more pronounced spreading
|
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• cells do not grow into a confluent monolayer and undergo rapidly initiated terminal differentiation
|
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal follicle morphogenesis and keratinocyte spreading and proliferation
|
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• patchy hair loss over the dorsal midline of the skull
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• less affected than in Itgb1tm1Ref/Itgb1tm1Ref Tg(KRT1-5-cre)5132Jlj mice
• however, no subepidermal blistering is observed
|
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• in a scratch wounding assay
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• complete resistant to DMBA/TPA-induced papillomas
|
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• DMBA-treated mutant mice displayed 9- to 13-fold net increase in the number of apoptotic basal keratinocytes compared to control
|
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• complete resistant to DMBA/TPA-induced papillomas
|
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• DMBA-treated mutant mice displayed 9- to 13-fold net increase in the number of apoptotic basal keratinocytes compared to control
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at P3 - P4
|
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• die exhibiting signs of acute dehydration
|
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• in skin grafted onto nude mice
|
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• epidermal hypocellularity develops in skin grafted onto nude mice
• fewer epidermal stem cells are present
|
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• develops in skin grafted onto nude mice
|
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• develops by P3 - P4
• no abnormal cell death is seen in these lesions
|
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• hyperproliferation and increased mitotic index in epidermal basal cells
|
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• after 10 - 15 days in culture keratinocytes fail to develop typical holoclones (corresponding to long term clonal outgrowth of epidermal stem cells)
|
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit markedly darkened ears relative to control mice
|
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• mice exhibit markedly darkened hair relative to control mice
|
|
• mice exhibit markedly darkened footpads relative to control mice
• Kitl mRNA expression is increased 5.5-fold in the footpad epidermis relative to control mice
|
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• mice exhibit markedly darkened tails relative to control mice
|
|
• mice exhibit markedly darkened ears relative to control mice
|
|
• mice exhibit markedly darkened hair relative to control mice
|
|
• mice exhibit markedly darkened footpads relative to control mice
• Kitl mRNA expression is increased 5.5-fold in the footpad epidermis relative to control mice
|
|
• mice exhibit markedly darkened tails relative to control mice
|
|
• mice exhibit markedly darkened footpads relative to control mice
• Kitl mRNA expression is increased 5.5-fold in the footpad epidermis relative to control mice
|
|
• mice exhibit markedly darkened tails relative to control mice
|
|
• mice exhibit markedly darkened ears relative to control mice
|
|
• mice exhibit markedly darkened ears relative to control mice
|
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• mice exhibit markedly darkened ears relative to control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• develop tumors in the skin, inner ear canal, and oral epithelium after 1 year of age, such that at 70 weeks of age, 42.9% and by 88 weeks of age, 72% of mice have tumors
|
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• develop tumors in the oral epithelium
|
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• develop tumors in the skin
|
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• majority of tumors are squamous cell carcinomas of the inner ear canal and oral epithelium
|
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• increase in basal keratinocyte proliferation
|
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• mutants exhibit increased epidermal proliferation and apoptosis, however epidermis appears histologically normal
|
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• develop tumors in the skin
|
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• increase in basal keratinocyte proliferation
|
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• develop tumors in the oral epithelium
|
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• develop tumors in the oral epithelium
|
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• develop tumors in the oral epithelium
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice delivered by Caesarian section do not survive beyond 24 hours after birth
|
| N |
• mice exhibit normal epidermal skin barrier function
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• fewer (6.25%) than the expected 12.5% of mutants were observed, indicating some lethality; time of analysis not specified
|
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• by 45 weeks of age, all mutants develop at least one skin tumor, with an average of four tumors per mouse
|
|
• skin tumors are all squamous cell carcinoma
|
|
• all mutants develop tumors by 45 weeks of age, significantly sooner than Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)1Jlj/0 mice or Brca1tm2Cxd/Brca1+ Tg(KRT5-cre)1Jlj/0 mice and by 70 weeks of age, 100% of mice exhibit tumors
|
|
• increase in basal keratinocyte proliferation
|
|
• mutants exhibit increased epidermal proliferation and apoptosis
|
|
• by 45 weeks of age, all mutants develop at least one skin tumor, with an average of four tumors per mouse
|
|
• increase in basal keratinocyte proliferation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• progressive loss of skin appendages
|
|
• progressive hair loss such that mice are hairless by 1 month of age
|
|
• mice develop epidermal hyperthickening combined with disorganization of the keratinocytes which progresses with age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• loss of sebaceous glands
|
|
• loss of sebaceous glands
|
|
• hair abnormalities
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• keratinocyte proliferation is mildly increased at P18 and is strongly increased in the back and tail skin at 3 months of age
(J:158802)
• however, keratinocytes in vitro show normal proliferation rate
(J:158802)
|
|
• transepidermal water loss is slightly increased at P18 and is significantly increased at 6 months of age, indicating disturbed epidermal barrier function
(J:158802)
|
|
• progressive skin inflammation, with a 60% increase in epidermal gamma-delta T cells, an increase in mast cells in the dermis, and increase in CD45+ alpha-beta and gamma-delta T cells in the dermis
(J:158802)
• however, macrophage or neutrophil infiltrate is not seen
(J:158802)
|
|
• loss of skin appendages
|
|
• sebaceous glands are virtually absent in the back skin of older mice
|
|
• progressive hair loss and mice are hairless by 2-4 months of age
(J:158802)
|
|
• hair follicles are abnormally shaped at P18 (first telogen)
|
|
• hair follicles are virtually absent in the back skin of older mice and only a few cysts are present in the dermis
|
|
• hair follicles are smaller at P18 (first telogen), but numbers are normal
|
|
• by P30, most follicles are in telogen compared to controls which have entered the second anagen
|
|
• a mild hypotrophy of the epidermis is seen at P5 (first anagen), but the dermis and appendages appear normal
• mice show only a rudimentary development of tight junctions in the epidermis
|
|
• bubble-like intercellular clefts between the keratinocytes of the stratum granulosum
|
|
• mice develop epidermal hyperthickening combined with disorganization of the keratinocytes at 2-3 months of age which progresses with age
(J:158802)
|
|
• fragile appearing skin
|
|
• fibrosis develops in the dermis
|
|
• sebaceous glands are virtually absent in the back skin of older mice
|
|
• keratinocyte proliferation is mildly increased at P18 and is strongly increased in the back and tail skin at 3 months of age
(J:158802)
• however, keratinocytes in vitro show normal proliferation rate
(J:158802)
|
|
• mast cells in young cells are degranulated, followed by a decrease in degranulated mast cells thereafter
|
|
• increase in mast cell number between P7 and P9 is greater in mutants than in controls and remains high unlike in controls which show a decrease over time
• higher number of mast cell progenitors in the white adipose tissue
|
|
• mice show enhanced levels of IgE in the dermis and in the serum
|
|
• mice show enhanced levels of IgG1 in the dermis
|
|
• mice show enhanced levels of IgG2a in the dermis
|
|
• transepidermal water loss is slightly increased at P18 and is significantly increased at 6 months of age, indicating disturbed epidermal barrier function
(J:158802)
|
|
• transient increase in mast cell chemokines in the epidermis and dermis
|
|
• mast cells in young cells are degranulated, followed by a decrease in degranulated mast cells thereafter
|
|
• increase in mast cell number between P7 and P9 is greater in mutants than in controls and remains high unlike in controls which show a decrease over time
• higher number of mast cell progenitors in the white adipose tissue
|
|
• mice show enhanced levels of IgE in the dermis and in the serum
|
|
• mice show enhanced levels of IgG1 in the dermis
|
|
• mice show enhanced levels of IgG2a in the dermis
|
|
• transient increase in mast cell chemokines in the epidermis and dermis
|
|
• progressive skin inflammation, with a 60% increase in epidermal gamma-delta T cells, an increase in mast cells in the dermis, and increase in CD45+ alpha-beta and gamma-delta T cells in the dermis
(J:158802)
• however, macrophage or neutrophil infiltrate is not seen
(J:158802)
|
|
• high consumption of drinking water
|
|
|
• all females are infertile
(J:158802)
|
|
|
• about 60% of males are infertile
(J:158802)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| atopic dermatitis | DOID:3310 |
OMIM:603165 OMIM:PS603165 |
J:221184 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• a significant deficit in sebaceous glands in 2-4 month-old mice
|
|
• primary keratinocytes isolated from mutant animals would not proliferate in culture
|
|
• a significant deficit in sebaceous glands in 2-4 month-old mice
|
|
• from approximately postnatal day 7 until P17, initial hair growth was sparse
• by P17, the pelage of mutant mice appeared identical to their normal littermates
|
|
• hair follicles are orientated randomly, rather than being arrayed in a hexagonal pattern as in control in P12 mice
|
|
• have consistently about 25% fewer hair follicles than control
|
|
• irregular hair cycle suggested by the presence of hair follicles in the hypodermis of P22 mice
• adult mutant mice periodically showed patches of receding hair, which lasted for several days, disappeared, and then appeared again at another location
|
|
• a thinner epidermis was evident in mutant mice at all ages
|
|
• primary keratinocytes isolated from mutant animals would not proliferate in culture
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit increased susceptibility to skin tumors induced by DMBA and TPA treatment compared to similarly treated wild-type mice
• pre-alignant tumors induced by DMBA and TPS exhibit increased growth rate compared to in similarly treated wild-type mice
• DMBA and TPA induced tumors exhibit earlier onset, faster progression to malignancy and increased volume compared to in tumors induced in wild-type mice
|
|
• tumors induced by DMBA and TPA treatment
|
|
• DMBA and TPA induced tumors exhibit earlier onset, faster progression to malignancy and increased volume compared to in tumors induced in wild-type mice
|
|
• 2 of 13 mice develop squamous cell carcinomas following treatment with DBMA and TPA unlike in wild-type mice
• DMBA and TPA induced tumors progress to malignant squamous cell carcinoma unlike in wild-type cells
|
| N |
• epidermal homeostasis is normal
|
|
• mice exhibit increased susceptibility to skin tumors induced by DMBA and TPA treatment compared to similarly treated wild-type mice
• pre-alignant tumors induced by DMBA and TPS exhibit increased growth rate compared to in similarly treated wild-type mice
• DMBA and TPA induced tumors exhibit earlier onset, faster progression to malignancy and increased volume compared to in tumors induced in wild-type mice
|
|
• tumors induced by DMBA and TPA treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no obvious abnormalities are seen at any stage of postnatal development
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 4.5 months, dermal cysts are detected
|
|
• 30% of 2 week old mice exhibit growth retardation
|
|
• at 4.5 months, dermal cysts are detected
|
|
• no hair shafts are observed in mutants
|
|
• no hair matrix is observed in mutants
|
|
• no inner root sheath is observed
|
|
• the stratum corneum extends deep into the hair follicles of mutants
|
|
• 2 week old mutants exhibit keratosis of the epidermis
|
|
• mutants older than 4 months show a significant widening of the intracellular space between keratinocytes in the epidermis
• some keratinocytes have long protrusions which contact neighboring keratinocytes
|
|
• 2-week old mutants exhibit strong hyperplasia of the epidermis
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 11/12/2024 MGI 6.24 |
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