Mouse Genome Informatics
cn1
    Braftm1Mmcm/Braf+
Ptentm1Mro/Ptentm1Mro
Tg(Tyr-cre/ERT2)1Lru/0

B6.Cg-Braftm1Mmcm Ptentm1Mro Tg(Tyr-cre/ERT2)1Lru
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• tamoxifen-treated mice must be euthanized between 40 and 70 days due to tumor load or ulceration

tumorigenesis
• tamoxifen-treated mice develop multiple heavily pigmented papules with an average latency of 18 days
• tamoxifen-treated mice exhibit metastasis in draining lymph nodes as early as 4 weeks after tumor induction
• however, no visceral metastasis is observed
• however, treatment with PLX4720 decreases tumor outgrowth
• in the absences of tamoxifen, most mice develop spontaneous melanomas due to leaky cre expression

integument
• in tamoxifen-treated mice
• tamoxifen-treated mice develop multiple heavily pigmented papules with an average latency of 18 days
• tamoxifen-treated mice exhibit metastasis in draining lymph nodes as early as 4 weeks after tumor induction
• however, no visceral metastasis is observed
• however, treatment with PLX4720 decreases tumor outgrowth
• in the absences of tamoxifen, most mice develop spontaneous melanomas due to leaky cre expression

Mouse Models of Human Disease
OMIM IDRef(s)
Melanoma, Cutaneous Malignant, Susceptibility to, 1; CMM1 155600 J:188523


Mouse Genome Informatics
cn2
    Braftm1Cpri/Braftm1Cpri
Cdkn2atm1Rdp/Cdkn2atm1Rdp
Tg(Tyr-cre/ERT2)1Lru/0

involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * DBA/2 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• tamoxifen-treated mice develop multiple tumors unlike Braftm1Cpri/Braftm1Cpri Tg(Tyr-cre/ERT2)1Laru mice that develop single tumors
• tamoxifen-treated mice develop nevi unlike control mice (either treated with only ethanol or lacking one of the alleles)
• 80% of tamoxifen-treated mice develop melanomas within 12 months
• median latency to develop melanomas in a tamoxifen-treated mouse is 7 months

integument
• tamoxifen-treated mice develop nevi unlike control mice (either treated with only ethanol or lacking one of the alleles)

homeostasis/metabolism
• tamoxifen-treated mice develop multiple tumors unlike Braftm1Cpri/Braftm1Cpri Tg(Tyr-cre/ERT2)1Laru mice that develop single tumors


Mouse Genome Informatics
cn3
    Braftm1Cpri/Braftm1Cpri
Tg(Tyr-cre/ERT2)1Lru/0

involves: 129P2/OlaHsd * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• tamoxifen-treated mice develop nevi most commonly at the site of application with some large melanocytic lesions around the perianal regions and in the eyelids unlike in control mice (either treated with only ethanol or lacking one of the alleles)
• nevi in tamoxifen-treated mice are slowly proliferating, dome-shaped outgrowths in the dermis composed of pigmented epithelioid or dendritic melanocytes with neuroid differentiation in some cases
• 80% of tamoxifen-treated mice develop eyelid nevi 3 to 5 months after treatment
• mice treated with high doses of tamoxifen develop perianal nevi 6 to 10 months after treatment
• 60% to 70% of tamoxifen-treated mice develop rapidly growing, invasive hypopigmented skin tumors that often (in 38% of mice) ulcerate the overlying epidermis, infiltrate the subcutis, skeletal muscle, and auricular cartilage and display characteristics of malignant melanomas
• some tamoxifen-treated mice develop oligomelanotic malignant melanomas unlike control mice (either treated with only ethanol or lacking one of the alleles)
• 54% of tamoxifen-treated mice develop melanomas within 12 months
• 64% of tamoxifen-treated mice develop melanomas after 14 months
• median latency to develop melanomas in a tamoxifen-treated mouse is 12 months

pigmentation
• following application of tamoxifen on the back, snouts, tails, ears, and paws are visibly darkened compared to in control mice (either treated with only ethanol or lacking one of the alleles)
• following application of tamoxifen on the back, 40% of mice develop darkened toenails proximal to the body on the front or hind feet unlike control mice
• following application of tamoxifen on the back, 50% of females develop darkened nipples unlike control mice
• following application of tamoxifen on the back, hairy skin is darkened most noticeable at the site of application unlike control mice

integument
• in 38% of tamoxifen-treated mice
• tamoxifen-treated mice develop nevi most commonly at the site of application with some large melanocytic lesions around the perianal regions and in the eyelids unlike in control mice (either treated with only ethanol or lacking one of the alleles)
• nevi in tamoxifen-treated mice are slowly proliferating, dome-shaped outgrowths in the dermis composed of pigmented epithelioid or dendritic melanocytes with neuroid differentiation in some cases
• 80% of tamoxifen-treated mice develop eyelid nevi 3 to 5 months after treatment
• mice treated with high doses of tamoxifen develop perianal nevi 6 to 10 months after treatment
• 60% to 70% of tamoxifen-treated mice develop rapidly growing, invasive hypopigmented skin tumors that often (in 38% of mice) ulcerate the overlying epidermis, infiltrate the subcutis, skeletal muscle, and auricular cartilage and display characteristics of malignant melanomas


Mouse Genome Informatics
cn4
    Braftm1Rima/Braf+
Krastm4Tyj/Kras+
Tg(Tyr-cre/ERT2)1Lru/0

involves: 129S4/SvJae * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• within 6 months, tamoxifen-treated mice develop large, rapid growing oligo-pigmented tumors with ulceration unlike wild-type mice
• tumors in tamoxifen-treated mice are largely composed of spindle cells with malignancy features

pigmentation
• within 2 to 3 months, tamoxifen-treated mice exhibit a darkening of the tails, ears, and paws compared with wild-type mice


Mouse Genome Informatics
cn5
    Braftm1Rima/Braf+
Tg(Tyr-cre/ERT2)1Lru/0

involves: C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
pigmentation
N
• mice exhibit normal pigmentation and do not develop nevi (J:161180)

tumorigenesis
N
• mice do not develop tumors (J:161180)


Mouse Genome Informatics
cn6
    Braftm1Rima/Braf+
Tg(GFP/KRAS2/ALPP)1Brn/0
Tg(Tyr-cre/ERT2)1Lru/0

involves: C57BL/6 * DBA/2 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• tamoxifen-treated mice exhibit rapid onset of melanoma with a median onset at 2 months and 100% penetrance within 3 months