Phenotypes associated with this allele
pigmentation
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• 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
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integument
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• 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
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(KRT14-rtTA)F42Efu mutation
(1 available)
Tg(tetO-EDN1,-lacZ)9Mhus mutation
(1 available)
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pigmentation
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N |
• following induction of Edn1 expression with Dox treatment during anagen, mice exhibit no premature hair graying phenotype at least by the 4th telogen
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• 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
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• 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
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• 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
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• 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
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integument
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• 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
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• 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
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cellular
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• 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
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• 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
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pigmentation
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• 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
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• 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
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• 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
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• 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
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integument
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• 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
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• 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
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cellular
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• 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
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• 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
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Myh6-tTA)6Smbf mutation
(4 available)
Tg(tetO-EDN1,-lacZ)9Mhus mutation
(1 available)
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mortality/aging
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• within 8 weeks of doxycycline withdrawal more than half of mice die
• however, mice fed doxycycline exhibit normal survival
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• fewer than expected mice are generated indicating fetal loss
• however, treatment with doxycycline restores normal survival
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cardiovascular system
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N |
• after doxycycline withdrawal, mice do not exhibit bradyarrhythmias or tachyarrhythmias
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• after doxycycline withdrawal
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• after doxycycline withdrawal
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• after doxycycline withdrawal, cardiomyocytes contain vesiculated nuclei unlike in wild-type cells
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• after doxycycline withdrawal
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• after doxycycline withdrawal
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• after doxycycline withdrawal, left ventricular endocardial circumference is increased compared to in wild-type mice
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• after doxycycline withdrawal
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• mild after doxycycline withdrawal
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• 5 weeks after doxycycline withdrawal
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• after doxycycline withdrawal
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• lengthened progressively over time after doxycycline withdrawal
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• 5 weeks after doxycycline withdrawal
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• after doxycycline withdrawal
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behavior/neurological
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• 5 weeks after doxycycline withdrawal
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• 5 weeks after doxycycline withdrawal
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respiratory system
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• after doxycycline withdrawal
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• 5 weeks after doxycycline withdrawal
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liver/biliary system
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• after doxycycline withdrawal
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muscle
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• after doxycycline withdrawal, cardiomyocytes contain vesiculated nuclei unlike in wild-type cells
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• after doxycycline withdrawal
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• after doxycycline withdrawal
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immune system
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• after doxycycline withdrawal
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growth/size/body
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• after doxycycline withdrawal
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cellular
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• after doxycycline withdrawal
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Analysis Tools