Phenotypes associated with this allele

• Allele Symbol: Tg(tetO-EDN1,-lacZ)9Mhus
• Allele Name: transgene insertion 9, Mansoor Husain
• Allele ID: MGI:4837732
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Mc1r^tm1.1Mymi/Mc1r^tm1.1Mymi Tg(KRT14-rtTA)F42Efu/0 Tg(tetO-EDN1,-lacZ)9Mhus/0 Tg(Tyr-cre/ERT2)13Bos/0	involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NTac * FVB	MGI:6269451
cn2	Tg(KRT14-rtTA)F42Efu/0 Tg(tetO-EDN1,-lacZ)9Mhus/0	involves: C57BL/6J * FVB	MGI:6269409
cn3	Ctnnb1^tm2Kem/Ctnnb1^tm2Kem Tg(KRT14-rtTA)F42Efu/0 Tg(tetO-EDN1,-lacZ)9Mhus/0 Tg(Tyr-cre/ERT2)13Bos/0	involves: C57BL/6J * FVB	MGI:6269417
cx4	Tg(Myh6-tTA)6Smbf/0 Tg(tetO-EDN1,-lacZ)9Mhus/0	involves: C57BL/6 * CBA	MGI:4837876

Genotype
MGI:6269451

cn1

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

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

pigmentation

abnormal epidermal melanocyte morphology ( J:231435 )

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

integument

abnormal epidermal melanocyte morphology ( J:231435 )

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

Genotype
MGI:6269409

cn2

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

pigmentation

pigmentation phenotype ( J:231435 )

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

abnormal melanocyte differentiation ( J:231435 )

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

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

abnormal melanocyte proliferation ( J:231435 )

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

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

ectopic hair follicle melanin granules ( J:231435 )

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

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

abnormal epidermal melanocyte morphology ( J:231435 )

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

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

integument

ectopic hair follicle melanin granules ( J:231435 )

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

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

abnormal epidermal melanocyte morphology ( J:231435 )

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

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

cellular

abnormal melanocyte differentiation ( J:231435 )

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

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

abnormal melanocyte proliferation ( J:231435 )

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

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

Genotype
MGI:6269417

cn3

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

pigmentation

abnormal melanocyte differentiation ( J:231435 )

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

abnormal melanocyte proliferation ( J:231435 )

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

abnormal coat/hair pigmentation ( J:231435 )

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

abnormal epidermal melanocyte morphology ( J:231435 )

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

integument

abnormal coat/hair pigmentation ( J:231435 )

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

abnormal epidermal melanocyte morphology ( J:231435 )

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

cellular

abnormal melanocyte differentiation ( J:231435 )

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

abnormal melanocyte proliferation ( J:231435 )

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

Genotype
MGI:4837876

cx4

• Allelic Composition: Tg(Myh6-tTA)6Smbf/0; Tg(tetO-EDN1,-lacZ)9Mhus/0
• Genetic Background: involves: C57BL/6 * CBA

mortality/aging

premature death ( J:131245 )

• within 8 weeks of doxycycline withdrawal more than half of mice die

• however, mice fed doxycycline exhibit normal survival

prenatal lethality, incomplete penetrance ( J:131245 )

• fewer than expected mice are generated indicating fetal loss

• however, treatment with doxycycline restores normal survival

cardiovascular system

cardiovascular system phenotype ( J:131245 )

N • after doxycycline withdrawal, mice do not exhibit bradyarrhythmias or tachyarrhythmias

liver vascular congestion ( J:131245 )

• after doxycycline withdrawal

pulmonary vascular congestion ( J:131245 )

• after doxycycline withdrawal

abnormal myocardial fiber morphology ( J:131245 )

• after doxycycline withdrawal, cardiomyocytes contain vesiculated nuclei unlike in wild-type cells

increased myocardial fiber size ( J:131245 )

• after doxycycline withdrawal

cardiac muscle necrosis ( J:131245 )

• after doxycycline withdrawal

abnormal ventricle endocardium morphology ( J:131245 )

• after doxycycline withdrawal, left ventricular endocardial circumference is increased compared to in wild-type mice

increased heart weight ( J:131245 )

• after doxycycline withdrawal

cardiac fibrosis ( J:131245 )

• mild after doxycycline withdrawal

decreased left ventricle systolic pressure ( J:131245 )

• 5 weeks after doxycycline withdrawal

prolonged P wave ( J:131245 )

• after doxycycline withdrawal

prolonged QRS complex duration ( J:131245 )

• lengthened progressively over time after doxycycline withdrawal

decreased systemic arterial systolic blood pressure ( J:131245 )

• 5 weeks after doxycycline withdrawal

heart inflammation ( J:131245 )

• after doxycycline withdrawal

behavior/neurological

hunched posture ( J:131245 )

• 5 weeks after doxycycline withdrawal

decreased locomotor activity ( J:131245 )

• 5 weeks after doxycycline withdrawal

respiratory system

pulmonary vascular congestion ( J:131245 )

• after doxycycline withdrawal

respiratory distress ( J:131245 )

• 5 weeks after doxycycline withdrawal

liver/biliary system

liver vascular congestion ( J:131245 )

• after doxycycline withdrawal

muscle

abnormal myocardial fiber morphology ( J:131245 )

• after doxycycline withdrawal, cardiomyocytes contain vesiculated nuclei unlike in wild-type cells

increased myocardial fiber size ( J:131245 )

• after doxycycline withdrawal

cardiac muscle necrosis ( J:131245 )

• after doxycycline withdrawal

immune system

heart inflammation ( J:131245 )

• after doxycycline withdrawal

growth/size/body

increased heart weight ( J:131245 )

• after doxycycline withdrawal