Analysis Tools
normal phenotype
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• mice are fertile and born at Mendelian ratios, but no further phenotypic analysis is provided
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Allele Symbol Allele Name Allele ID |
Braftm1Mmcm targeted mutation 1, Martin McMahon MGI:3711771 |
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| Summary |
24 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are fertile and born at Mendelian ratios, but no further phenotypic analysis is provided
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 7-8 weeks after adenoviral Cre intranasal administration to 6- to 8-week old mutants, treated animals are euthanized because they show labored breathing and general wasting
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• cellular origins of cancerous are ambiguous aslesions are Clara Cell antigen-negative, but majority of cells express Surfactant protein C as early as 2 weeks after Cre treatment (CCA and SP-C are both markers of alveolar type II pneumocytes)
• 4 weeks after Cre treatment, mice are treated for 28 days with a pharmacological inhibitor of MEK1/2 which prevents almost all tumor development, while vehicle-treated animals show numerous lung tumors
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• 7 weeks after high dose Cre treatment, evidence of multiple adenomatous tumor formation is present in mouse lungs, while no tumors are detected in untreated mice after 6 months
• papillary adenomas are detected 6-8 weeks after lower dose adenoviral Cre treatment; lesions seem to increase in size and number
• lesions arise in alveolar ducts expanding outward and around broncioles
• at ~14 weeks, papillary adenomas undergo changes at periphery; cells change such that they have more cytoplasm and become eosinophilic
• after lower dose Cre treatement, adenomas do not grow beyond ~900 um in diameter
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• only 2 mice (of 57) that develop adenomas show evidence of progression to adenocarcinoma; cells from these mice display nuclear enlargement, hyperchromasia, and contour irregularities
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• cellular origins of cancerous are ambiguous aslesions are Clara Cell antigen-negative, but majority of cells express Surfactant protein C as early as 2 weeks after Cre treatment (CCA and SP-C are both markers of alveolar type II pneumocytes)
• 4 weeks after Cre treatment, mice are treated for 28 days with a pharmacological inhibitor of MEK1/2 which prevents almost all tumor development, while vehicle-treated animals show numerous lung tumors
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• 7 weeks after high dose Cre treatment, evidence of multiple adenomatous tumor formation is present in mouse lungs, while no tumors are detected in untreated mice after 6 months
• papillary adenomas are detected 6-8 weeks after lower dose adenoviral Cre treatment; lesions seem to increase in size and number
• lesions arise in alveolar ducts expanding outward and around broncioles
• at ~14 weeks, papillary adenomas undergo changes at periphery; cells change such that they have more cytoplasm and become eosinophilic
• after lower dose Cre treatement, adenomas do not grow beyond ~900 um in diameter
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• only 2 mice (of 57) that develop adenomas show evidence of progression to adenocarcinoma; cells from these mice display nuclear enlargement, hyperchromasia, and contour irregularities
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• 4 weeks after Cre administration, lung epithelium hyperplasia is observed
• at earlier times after Cre treatment, hyperplastic epithelium shows papillary outgrowths, but these were not seen at earlier time points (2-4 weeks post-treatment)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice with surgical delivery of a cre-expressing adenovirus to the adult thyroid gland develop papillary thyroid carcinoma
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• mice with surgical delivery of a cre-expressing adenovirus to the adult thyroid gland develop papillary thyroid carcinoma
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tamoxifen-treated mice must be euthanized between 40 and 70 days due to tumor load or ulceration
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• in tamoxifen treated mice
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• 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
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• in tamoxifen-treated mice
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• 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
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tamoxifen-treated mice show accelerated tumorigenesis of unpigmented, nonmetastatic melanoma compared to single Braf conditional mutants
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop extensive papillary thyroid carcinomas by 12 months of tamoxifen treatment, first showing enlarged follicles within 7 days of tamoxifen treatment, a squamous morphology of thyrocytes accompanied by a large increase in follicle size and loss of colloid by 14 days of tamoixfen treatment, and tumor cells with characteristic papillary structure by 6 months of tamoxifen administration
• occasionally localized tumor invasion into the surrounding muscle is seen, however frank metastasis to lymph nodes or distant organs is not observed
• although mice have palpable thyroid tumors by 13 months of tamoxifen treatment, mice are not overtly sick
• mice not treated with tamoxifen show regions of papillary thyroid cancer with adjacent histologically normal thyroid architecture at 12 months of age, however these mice exhibit normal TSH and T4 levels
• treatment with PD0325901, an MEK1/2 inhibitor, results in regression of papillary thyroid cancer in tamoxifen-administered mutants
• treatment with PD0325901 and T3 results in further papillary thyroid cancer regression in tamoxifen-administered mutants
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• mice not treated with tamoxifen exhibit increased thyroid volume, however thyroid architecture is normal, indicating some leakiness of the cre transgene
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• within 7 days of tamoxifen treatment, mice show enlarged follicles throughout the entire gland
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• tamoxifen treated mice develop an enlarged, goiterous, hypercellular thyroid that is up to 10 times larger than controls at 1 month and up to 300 times larger at 12 months after tamoxifen treatment
• treatment with PD0325901 leads to decreased thyroid size of tamoxifen-administered mice
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• mice develop extensive papillary thyroid carcinomas by 12 months of tamoxifen treatment, first showing enlarged follicles within 7 days of tamoxifen treatment, a squamous morphology of thyrocytes accompanied by a large increase in follicle size and loss of colloid by 14 days of tamoixfen treatment, and tumor cells with characteristic papillary structure by 6 months of tamoxifen administration
• occasionally localized tumor invasion into the surrounding muscle is seen, however frank metastasis to lymph nodes or distant organs is not observed
• although mice have palpable thyroid tumors by 13 months of tamoxifen treatment, mice are not overtly sick
• mice not treated with tamoxifen show regions of papillary thyroid cancer with adjacent histologically normal thyroid architecture at 12 months of age, however these mice exhibit normal TSH and T4 levels
• treatment with PD0325901, an MEK1/2 inhibitor, results in regression of papillary thyroid cancer in tamoxifen-administered mutants
• treatment with PD0325901 and T3 results in further papillary thyroid cancer regression in tamoxifen-administered mutants
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• mice develop hypothyroidism by 1-3 months of tamoxifen treatment
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• 100-fold increase in serum TSH levels at 1 and 3 months of tamoxifen treatment
• mice not treated with tamoxifen exhibit normal levels of TSH
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• mice exhibit a decrease in serum T4 levels at 1 and 3 months of tamoxifen treatment
• mice not treated with tamoxifen exhibit normal T4 levels
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| thyroid gland papillary carcinoma | DOID:3969 |
OMIM:188550 |
J:172205 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Cre-treated mice show scattered papillary adenomas with evidence of subpleural nodules harboring cords of atypical cells trapped within regions of mesenchymal proliferation
• 2/4 mice display multiple lung tumors with a bronchioalveolar component
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• Cre-treated mice show scattered papillary adenomas with evidence of subpleural nodules harboring cords of atypical cells trapped within regions of mesenchymal proliferation
• 2/4 mice display multiple lung tumors with a bronchioalveolar component
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 8 weeks after adenoCre treatment, lungs show rapid cancer progression with increased proliferation compared to Trp53-sufficient mice
• tumors show nodules composed of central papillary structures with solid peripheral areas
• all double mutants show increased proliferation, and cells show altered nuclear morphology, while Trp53 conditional single mutants have normal lung phenotypes
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• 2/5 mice are found to have prominent adenocarcinomas, composed of glandular structures lined by atypical cells with enlarged nuclei, hyperchromasia, contour irregularities, and prominent nucleoli
• large areas of necrosis are present in adenocarcinomas, with evidence of lymphatic and vascular invasion
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• 8 weeks after adenoCre treatment, lungs show rapid cancer progression with increased proliferation compared to Trp53-sufficient mice
• tumors show nodules composed of central papillary structures with solid peripheral areas
• all double mutants show increased proliferation, and cells show altered nuclear morphology, while Trp53 conditional single mutants have normal lung phenotypes
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• 2/5 mice are found to have prominent adenocarcinomas, composed of glandular structures lined by atypical cells with enlarged nuclei, hyperchromasia, contour irregularities, and prominent nucleoli
• large areas of necrosis are present in adenocarcinomas, with evidence of lymphatic and vascular invasion
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• 8 weeks after Cre treatment, some small airways display papillary hyperplasia, not seen in Braf-conditional mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 7-10 days following 4-hydroxytamoxifen (4-HT) treatment, all mice show expansion of highly pigmented cells that develop into pigmented malignant lesions in locations of 4-HT administration such as the face, flank, or tail skin
• pigmented melanoma cells are seen throughout the dermis and subcutis of 4-HT treated mice and show pagetoid spread into the epidermis
• lesions in 4-HT treated mice progress rapidly to advanced malignancy such that all mice require euthanasia 25-50 days following 4-HT administration
• treatment of 4-HT treated mice with the MEK1/2 inhibitor PD325901 or the mTorc1 inhibitor rapamycin inhibits melanoma formation
• mice in which drug treatment is ceased subsequently develop malignant melanoma
• mice treated once with PD325901 to prevent melanoma remain sensitive to the anti-melanoma action of a second round of PD325901 administration
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• 7-10 days following 4-hydroxytamoxifen (4-HT) treatment, all mice show expansion of highly pigmented cells that develop into pigmented malignant lesions in locations of 4-HT administration such as the face, flank, or tail skin
• pigmented melanoma cells are seen throughout the dermis and subcutis of 4-HT treated mice and show pagetoid spread into the epidermis
• lesions in 4-HT treated mice progress rapidly to advanced malignancy such that all mice require euthanasia 25-50 days following 4-HT administration
• treatment of 4-HT treated mice with the MEK1/2 inhibitor PD325901 or the mTorc1 inhibitor rapamycin inhibits melanoma formation
• mice in which drug treatment is ceased subsequently develop malignant melanoma
• mice treated once with PD325901 to prevent melanoma remain sensitive to the anti-melanoma action of a second round of PD325901 administration
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• spread of melanoma in 4-HT treated mice is seen into the regional draining lymph nodes in 100% of mice and to the lungs in some cases
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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:151023 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 4-HT treated mice eventually develop focal malignant melanomas
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• 4-HT treated mice eventually develop focal malignant melanomas
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• 4-hydroxytamoxifen (4-HT) treated mice initially develop benign melanocytic lesions but they eventually develop focal malignant melanomas
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants develop lethal prostate cancer 4 months after tamoxifen induction
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• mutants develop lethal prostate cancer 4 months after tamoxifen induction
• tumors are large and highly proliferative and are primarily composed of luminal epithelial cells
• tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration
• tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative
• treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation
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• tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction
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• tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction
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• metastases to lungs and lymph nodes are seen in tamoxifen treated mutants and disseminated tumor cells are seen in the bone marrow
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• mutants develop lethal prostate cancer 4 months after tamoxifen induction
• tumors are large and highly proliferative and are primarily composed of luminal epithelial cells
• tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration
• tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative
• treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation
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• tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction
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• tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction
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• mutants develop lethal prostate cancer 4 months after tamoxifen induction
• tumors are large and highly proliferative and are primarily composed of luminal epithelial cells
• tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration
• tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative
• treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation
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• tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction
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• tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| prostate cancer | DOID:10283 |
OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959 |
J:191327 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increase in number of mainly MHC II+CD11c+ dendritic cells in the liver
• however, the number of dendritic cells in the lung and total numbers of macrophages, NK cells, B cells, and T cells are unaffected and mice do not exhibit anemia or alternation of circulating blood dendritic cells numbers
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• increase in number of mainly MHC II+CD11c+ dendritic cells in the liver
• however, the number of dendritic cells in the lung and total numbers of macrophages, NK cells, B cells, and T cells are unaffected and mice do not exhibit anemia or alternation of circulating blood dendritic cells numbers
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• by 12 weeks of age, mice develop small inflammatory infiltrates mainly to the liver that progressively increase in size with age
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• by 20 weeks of age, all mice show small lesions in the lung
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• by 12 weeks of age, mice develop small inflammatory infiltrates mainly to the liver that progressively increase in size with age
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• by 20 weeks of age, all mice show small lesions in the lung
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Langerhans-cell histiocytosis | DOID:2571 |
OMIM:246400 OMIM:604856 |
J:211690 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tamoxifen treated mice exhibit accelerated progression to poorly differentiated thyroid carcinoma and overt undifferentiated anaplastic thyroid carcinoma with highly pleomorphic, atypical cells with evidence of necrosis
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• tamoxifen treated mice exhibit accelerated progression to poorly differentiated thyroid carcinoma and overt undifferentiated anaplastic thyroid carcinoma with highly pleomorphic, atypical cells with evidence of necrosis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice administered tamoxifen develop papillary thyroid carcinomas
• tumors show both papillary growth morphology and nuclear features of papillary thyroid carcinoma
• even with very long latency, extrathyroidal invasion is not seen and cervical lymph node metastases are not seen
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• mice administered tamoxifen develop papillary thyroid carcinomas
• tumors show both papillary growth morphology and nuclear features of papillary thyroid carcinoma
• even with very long latency, extrathyroidal invasion is not seen and cervical lymph node metastases are not seen
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• tamoxifen treated mice generally succumb to respiratory compromise due to tracheal compression by large noninvasive tumors
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tamoxifen treated mice exhibit shortened survival
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• tamoxifen treated mice develop large papillary thyroid carcinoma that exhibit features associated with aggressive behavior including solid growth, tall cell morphology, focal necrosis, and hobnail features
• about 50% of mice with papillary thyroid carcinoma acquire poorly differentiated thyroid carcinoma or undifferentiated anaplastic thyroid carcinoma
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• tamoxifen treated mice develop large papillary thyroid carcinoma that exhibit features associated with aggressive behavior including solid growth, tall cell morphology, focal necrosis, and hobnail features
• about 50% of mice with papillary thyroid carcinoma acquire poorly differentiated thyroid carcinoma or undifferentiated anaplastic thyroid carcinoma
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• median survival of about 6 months following tumor induction with tamoxifen
• tumor induced mice treated with the BRAF inhibitor PLX4720 show improved survival
• tumor induced mice treated with both the BRAF inhibitor PLX4720 and the selective MEK inhibitor PD0325901show prolonged survival
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• tamoxifen treated mice exhibit accelerated progression from papillary thyroid carcinoma to poorly differentiated thyroid carcinoma and overt undifferentiated anaplastic thyroid carcinoma with highly pleomorphic, atypical cells with evidence of necrosis
• carcinoma in tamoxifen treated mice shows tracheal invasion and extrathyroidal extension
• marker analysis indicates that anaplastic thyroid carcinoma in tamoxifen treated mice originates from thyroid epithelium
• tumors from tamoxifen treated mice exhibit very slow initial growth upon induction but rapid tumor growth after a variable latency
• mice supplemented with L-thyroxine immediately following tamoxifen administration show suppressed TSH levels and develop anaplastic thyroid carcinoma with a similar latency as unsupplemented controls
• anaplastic thyroid carcinomas exhibit a gene expression profile of high-grade, undifferentiated carcinomas
• tumor induced mice treated with the BRAF inhibitor PLX4720 show improved survival and a decrease in contralateral papillary thyroid carcinomas, however no decrease in anaplastic thyroid carcinoma size is seen and tumors even grow larger
• tumor induced mice treated with both the BRAF inhibitor PLX4720 and the selective MEK inhibitor PD0325901 show complete regression of tumors and prolonged survival
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• 19% of tamoxifen treated mice exhibit lung metastases
• however, region lymph node metastases are not seen
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• tamoxifen treated mice exhibit accelerated progression from papillary thyroid carcinoma to poorly differentiated thyroid carcinoma and overt undifferentiated anaplastic thyroid carcinoma with highly pleomorphic, atypical cells with evidence of necrosis
• carcinoma in tamoxifen treated mice shows tracheal invasion and extrathyroidal extension
• marker analysis indicates that anaplastic thyroid carcinoma in tamoxifen treated mice originates from thyroid epithelium
• tumors from tamoxifen treated mice exhibit very slow initial growth upon induction but rapid tumor growth after a variable latency
• mice supplemented with L-thyroxine immediately following tamoxifen administration show suppressed TSH levels and develop anaplastic thyroid carcinoma with a similar latency as unsupplemented controls
• anaplastic thyroid carcinomas exhibit a gene expression profile of high-grade, undifferentiated carcinomas
• tumor induced mice treated with the BRAF inhibitor PLX4720 show improved survival and a decrease in contralateral papillary thyroid carcinomas, however no decrease in anaplastic thyroid carcinoma size is seen and tumors even grow larger
• tumor induced mice treated with both the BRAF inhibitor PLX4720 and the selective MEK inhibitor PD0325901 show complete regression of tumors and prolonged survival
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• small increase in TSH levels (less than 10-fold elevation) in tamoxifen treated mice
• mice supplemented with L-thyroxine immediately following tamoxifen administration show suppressed TSH levels
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• tamoxifen treated mice quickly deteriorate after progression to anaplastic thyroid carcinoma, with rapidly growing neck masses and development of audible respiratory stridor
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 7-10 days following 4-hydroxytamoxifen (4-HT) treatment, all mice show expansion of highly pigmented cells that develop into pigmented malignant lesions in locations of 4-HT administration such as the face, flank, or tail skin
• pigmented melanoma cells are seen throughout the dermis and subcutis of 4-HT treated mice and show pagetoid spread into the epidermis
• lesions in 4-HT treated mice progress rapidly to advanced malignancy such that all mice require euthanasia 25-50 days following 4-HT administration
• treatment of 4-HT treated mice with the MEK1/2 inhibitor PD325901 or the mTorc1 inhibitor rapamycin inhibits melanoma formation
• mice in which drug treatment is ceased subsequently develop malignant melanoma
• mice treated once with PD325901 to prevent melanoma remain sensitive to the anti-melanoma action of a second round of PD325901 administration
• treatment of melanoma bearing mice with either PD325901 or rapamycin inhibits further tumor growth but has little or no effect on tumor regression
• treatment of melanoma bearing with both PD325901 or rapamycin results in a 20% reduction in tumor size
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• 7-10 days following 4-hydroxytamoxifen (4-HT) treatment, all mice show expansion of highly pigmented cells that develop into pigmented malignant lesions in locations of 4-HT administration such as the face, flank, or tail skin
• pigmented melanoma cells are seen throughout the dermis and subcutis of 4-HT treated mice and show pagetoid spread into the epidermis
• lesions in 4-HT treated mice progress rapidly to advanced malignancy such that all mice require euthanasia 25-50 days following 4-HT administration
• treatment of 4-HT treated mice with the MEK1/2 inhibitor PD325901 or the mTorc1 inhibitor rapamycin inhibits melanoma formation
• mice in which drug treatment is ceased subsequently develop malignant melanoma
• mice treated once with PD325901 to prevent melanoma remain sensitive to the anti-melanoma action of a second round of PD325901 administration
• treatment of melanoma bearing mice with either PD325901 or rapamycin inhibits further tumor growth but has little or no effect on tumor regression
• treatment of melanoma bearing with both PD325901 or rapamycin results in a 20% reduction in tumor size
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• spread of melanoma is seen into the regional draining lymph nodes in 100% of mice and to the lungs in some cases
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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:151023 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• decrease in lifespan
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• severe hepatosplenomegaly
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• lesions are associated with massive increase of MHC II+CD11c+ dendritic cells
• expansion of blood circulating dendritic cell precursors and blood circulating dendritic cells
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• histiocytic infiltrates in the skin, liver, spleen, and lungs by 8 weeks of age, resulting in a broad destruction of tissue architecture by 16 weeks of age
• histiocytic lesions exhibit classical granulomatous organization, including multinucleated giant cell formation
• granuloma lesions contain massive CD11c+ langerin+ infiltrates, a large number of macrophages, NK cells, B cells, and T cells, with a specific accumulation of regulatory T cells
• local fibrotic response is seen within the granulomas and surrounding stroma
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• mice rapidly develop an aggressive Langerhans-cells histiocytosis-like disease with 100% penetrance
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• granuloma lesions are associated with an increase in several chemokines and cytokines (Ccl2, Ccl15, Il6, Il10, IFN-gamma, and TGF-beta) indicative of a local cytokine storm
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• severe hepatosplenomegaly
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• lesions are associated with massive increase of MHC II+CD11c+ dendritic cells
• expansion of blood circulating dendritic cell precursors and blood circulating dendritic cells
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• severe hepatosplenomegaly
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• severe hepatosplenomegaly
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Langerhans-cell histiocytosis | DOID:2571 |
OMIM:246400 OMIM:604856 |
J:211690 | |
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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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• with induction of Cre expression from the transgene, multiple adenomatous tumors form in mouse lungs
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• with induction of Cre expression from the transgene, multiple adenomatous tumors form in mouse lungs
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• topical administration of 4-hydroxytamoxifen (4-HT) to the ear, tail or flank results in the development of benign melanocytic hyperplasias that are larger and more highly pigmented than in conditional heterozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• pigmented lesions in 4-HT treated mice are frequently located at the dermal-epidermal junction with extension into the dermis, indicating melanocytic nevi
• other melanocytic proliferations form in the dermis with no junctional component in 4-HT treated mice
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• mice treated with 4-hydroxytamoxifen (4-HT) either topically or systemically develop highly pigmented lesions that are detected by 21-28 days after 4-HT administration; these are small papular pigmented lesions that are not malignant
• topical administration of high concentrations of 4-HT occasionally results in periocular lesions on the face and on the glabrous skin of the paws
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit low birth weight and fail to thrive
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• when cultured on fibronectin-coated plates, inter-follicular epidermis melanocytes exhibit increased survival compared with wild-type mice
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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 04/23/2024 MGI 6.23 |
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