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Phenotypes Associated with This Genotype
Genotype
MGI:6259566
Allelic
Composition
Cdk4tm1.1Bbd/Cdk4tm1.1Bbd
Tg(Mt1-HGFSF)#Lmb/0
Genetic
Background
B6.Cg-Cdk4tm1.1Bbd Tg(Mt1-HGFSF)#Lmb
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdk4tm1.1Bbd mutation (0 available); any Cdk4 mutation (30 available)
Tg(Mt1-HGFSF)#Lmb mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• in a 2-step (DMBA/TPA) skin carcinogenesis protocol, all (16 of 16) mice show melanocytic nevi within the first weeks of life while still under TPA treatment
• all DMBA/TPA-treated mice develop widespread, rapidly growing skin melanomas and have to be sacrificed by 12 weeks of age due to melanomas >10 mm in diameter and systemic signs of illness; an average of ~48 cutaneous melanomas is observed
• DMBA/TPA-induced melanomas involve the epidermo-dermal junction and show vertical invasive growth into the dermis; at 12 weeks of age, vertical tumor thickness is larger than that in Cdk4tm1.1Bbd/Cdk4+ Tg(Mt1-HGFSF)#Lmb/0 mice
• heavily pigmented epitheloid melanoma cells are arranged in bands and nests between lightly pigmented spindle-shaped melanoma cells
• only 3 of 16 DMBA/TPA-treated mice develop a single papilloma in skin
• at 30 weeks of age, untreated mice exhibit a similar number of melanocytic nevi in skin as untreated Tg(Mt1-HGFSF)#Lmb/0 mice
• untreated mice develop single, rapidly growing, spontaneous skin melanomas starting at ~30-40 weeks of age; ~20% of these mice have to be sacrificed by 1 year of age, with primary melanomas >10 mm in diameter
• all DMBA/TPA-treated mice develop rapidly growing skin melanomas reaching >10 mm in diameter at 12 weeks of age
• few mitoses and a low % of Ki67 staining are noted in spindle-shaped melanoma cells near the invasion front, indicating proliferative activity of melanoma cells
• DMBA/TPA-treated mice show locoregional metastatic growth of melanoma cells in the draining lymph nodes as well as numerous melanoma micrometastases in lung tissue
• in lymph nodes of DMBA/TPA-treated mice, melanoma cells are mostly spindle-shaped cells with little/no melanin that eventually disrupt lymph node architecture and displace lymphoid cells; however, heavily pigmented epitheloid melanoma cells are also observed
• in DMBA/TPA-treated mice, the average number of lung metastases is significantly higher than that in DMBA/TPA-treated Cdk4tm1.1Bbd/Cdk4+ Tg(Mt1-HGFSF)#Lmb/0 mice
• untreated mice with large spontaneous primary melanomas arising in skin also show locoregional metastases in adjacent draining lymph nodes as well as distal micrometastases in the lungs

integument
• at 30 weeks of age, untreated mice exhibit a similar number of melanocytic nevi in skin as untreated Tg(Mt1-HGFSF)#Lmb/0 mice
• untreated mice develop single, rapidly growing, spontaneous skin melanomas starting at ~30-40 weeks of age; ~20% of these mice have to be sacrificed by 1 year of age, with primary melanomas >10 mm in diameter

immune system
• at sacrifice, DMBA/TPA-treated mice show heavily pigmented axillary lymph nodes
• at sacrifice, DMBA/TPA-treated mice show enlarged axillary lymph nodes due to growth of melanoma cells
• at sacrifice, DMBA/TPA-treated mice show heavily pigmented inguinal lymph nodes
• at sacrifice, DMBA/TPA-treated mice show enlarged inguinal lymph nodes due to growth of melanoma cells

homeostasis/metabolism
• in a 2-step (DMBA/TPA) skin carcinogenesis protocol, all (16 of 16) mice show melanocytic nevi within the first weeks of life while still under TPA treatment
• all DMBA/TPA-treated mice develop widespread, rapidly growing skin melanomas and have to be sacrificed by 12 weeks of age due to melanomas >10 mm in diameter and systemic signs of illness; an average of ~48 cutaneous melanomas is observed
• DMBA/TPA-induced melanomas involve the epidermo-dermal junction and show vertical invasive growth into the dermis; at 12 weeks of age, vertical tumor thickness is larger than that in Cdk4tm1.1Bbd/Cdk4+ Tg(Mt1-HGFSF)#Lmb/0 mice
• heavily pigmented epitheloid melanoma cells are arranged in bands and nests between lightly pigmented spindle-shaped melanoma cells
• only 3 of 16 DMBA/TPA-treated mice develop a single papilloma in skin


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
03/13/2019
MGI 6.13
The Jackson Laboratory