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Allele Symbol Allele Name Allele ID |
Cdk4tm1.1Bbd targeted mutation 1.1, Mariano Barbacid MGI:2154521 |
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| Summary |
8 genotypes
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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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• weigh 5 - 10% more than wild-type or heterozygous littermates
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• the pancreatic islet area is increased 7-10 fold, primarily die to increased beta-cell number, and resemble insulinomas
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• increased population of testicular Leydig cells
• normal architecture of seminiferous tubules
• normal germ- and Sertoli-cell development in the testes
• males and females were fertile
• normal female reproductive organs
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| N |
• normal glucose levels
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• increased population of testicular Leydig cells
• normal architecture of seminiferous tubules
• normal germ- and Sertoli-cell development in the testes
• males and females were fertile
• normal female reproductive organs
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• pancreatic islet hyperplasia due to increased beta-cell number, but to a lesser extent than in homozygous mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at 8-15 weeks after DMBA treatment, mice exhibit significantly increased melanoma multiplicity relative to control mice, with primary melanomas invading the dermis and showing tumor-associated angiogenesis
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• less than 15 weeks after DMBA treatment, mice show increased incidence of distal melanoma metastases in the lungs relative to control mice (57.1% versus 16.7%)
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• in DMBA-treated mice, primary melanomas show an increased proliferative index, with a significantly higher number of PCNAhigh melanoma cells relative to control mice, consistent with increased melanoma multiplicity
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• at 8-15 weeks after DMBA treatment, mice exhibit significantly increased melanoma multiplicity relative to control mice, with primary melanomas invading the dermis and showing tumor-associated angiogenesis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• latency to develop lung adenomas is significantly shorter compared to double mutants wild-type for Cdk4; however development of tumors characteristic of Cdk4tm1.1Bbd mutant mice is not accelerated
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• histiocytic sarcoma and other sarcomas are seen
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• anal papillomas are seen
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• focal metaplasia in the pancreatic ducts consisting of tall columnar cells with abundant apical mucin resembling gastric surface epithelial cells
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• focal metaplasia in the pancreatic ducts consisting of tall columnar cells with abundant apical mucin resembling gastric surface epithelial cells
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• latency to develop lung adenomas is significantly shorter compared to double mutants wild-type for Cdk4; however development of tumors characteristic of Cdk4tm1.1Bbd mutant mice is not accelerated
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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• at 30 weeks of age, untreated mice exhibit a similar number of melanocytic nevi in skin as untreated Tg(Mt1-HGFSF)#Lmb/0 mice
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• 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
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• 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
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• 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
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• at 30 weeks of age, untreated mice exhibit a similar number of melanocytic nevi in skin as untreated Tg(Mt1-HGFSF)#Lmb/0 mice
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• 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
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• at sacrifice, DMBA/TPA-treated mice show heavily pigmented axillary lymph nodes
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• at sacrifice, DMBA/TPA-treated mice show enlarged axillary lymph nodes due to growth of melanoma cells
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• at sacrifice, DMBA/TPA-treated mice show heavily pigmented inguinal lymph nodes
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• at sacrifice, DMBA/TPA-treated mice show enlarged inguinal lymph nodes due to growth of melanoma cells
|
|
• 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
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| skin melanoma | DOID:8923 |
OMIM:608035 OMIM:612263 |
J:111992 | |
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in a 2-step (DMBA/TPA) skin carcinogenesis protocol, all (15 of 15) mice develop progressively growing melanomas and have to be sacrificed between 14 and 16 weeks of age with an average of 32 cutaneous melanomas
• DMBA/TPA-induced melanomas involve the epidermo-dermal junction and show vertical invasive growth in the underlying dermis
• only 3 of 15 DMBA/TPA-treated mice develop a single papilloma in skin
|
|
• DMBA/TPA-treated mice show locoregional metastatic growth of melanoma cells in 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 comparable to that in Tg(Mt1-HGFSF)#Lmb/0 mice
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• DMBA/TPA-induced melanomas grow with a slight delay relative to those in Cdk4tm1.1Bbd/Cdk4tm1.1Bbd Tg(Mt1-HGFSF)#Lmb/0 mice
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• 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
|
|
• in a 2-step (DMBA/TPA) skin carcinogenesis protocol, all (15 of 15) mice develop progressively growing melanomas and have to be sacrificed between 14 and 16 weeks of age with an average of 32 cutaneous melanomas
• DMBA/TPA-induced melanomas involve the epidermo-dermal junction and show vertical invasive growth in the underlying dermis
• only 3 of 15 DMBA/TPA-treated mice develop a single papilloma in skin
|
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• spontaneous development of malignant melanoma by 300 days of age in all mice
• malignant melanomas have the appearance of nodular lesions and tumors show larger and more pleomorphic nuclei, abundant cytoplasm and numerous multinucleated giant cells and low levels of Ki-67 staining
• two distinct malignant melanoma subtypes are seen: 55% of melanomas are in the deep dermis, separated from the naevus cells above by layers of collagen, while 42% of lesions encompass the subepidermal location of the naevi and appear to be expanded naevi, although cells have morphological features of malignancy
• majority of tumors are located on the back
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• mice develop malignant melanoma by 200 days of age after a single neonatal UVB dose
• melanocyte migration from the follicular outer root sheath into the epidermis after neonatal UV radiation is normal
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• mice develop dermal melanocyte proliferations that are similar to superficial cogenital naevi
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• neonates exhibit a higher number of dermal melanocytes
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• naevi are nearly always observed immediately beneath the epidermis in a band-like distribution, reminiscent of naevus cells, above lesions
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• spontaneous development of malignant melanoma by 300 days of age in all mice
• malignant melanomas have the appearance of nodular lesions and tumors show larger and more pleomorphic nuclei, abundant cytoplasm and numerous multinucleated giant cells and low levels of Ki-67 staining
• two distinct malignant melanoma subtypes are seen: 55% of melanomas are in the deep dermis, separated from the naevus cells above by layers of collagen, while 42% of lesions encompass the subepidermal location of the naevi and appear to be expanded naevi, although cells have morphological features of malignancy
• majority of tumors are located on the back
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• mice develop dermal melanocyte proliferations that are similar to superficial cogenital naevi
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| skin melanoma | DOID:8923 |
OMIM:608035 OMIM:612263 |
J:222847 | |
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 04/16/2024 MGI 6.23 |
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