|
Allele Symbol Allele Name Allele ID |
Gt(ROSA)26Sortm1(cre/ERT)Nat targeted mutation 1, Jeremy Nathans MGI:2669525 |
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| Summary |
42 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with tamoxifen exhibit a dosage and frequency dependent lethality dieing by 16 months unlike in mice lacking cre expression
|
|
• all mice develop tumors in the juxta-articular region in the limbs with some evidence of calcification
• following tamoxifen treatment, all mice develop tumors in the juxta-articular region in the limbs with some evidence of calcification
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• mice develop synovial sarcomas
• following tamoxifen treatment, mice develop synovial sarcomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| synovial sarcoma | DOID:5485 |
OMIM:300813 |
J:147728 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• hematopoietic stem and progenitor cells (HSPCs) of mice treated with tamoxifen do not exhibit a selective advantage over cells not expressing the modified cDNA
• the total number of HSPCs is normal in irradiated mice
|
|
• following irradiation, the proportion of GFP+ cells in the hematopoietic stem and progenitor cell compartment and myeloid and lymphoid lineages of tamoxifen-treated mice is increased compared to un-irradiated mice
• GFP+ cell accumulation occurs whether mice are treated with tamoxifen 2 or 7 days after irradiation
• however, no competitive advantage is observed when mice are treated with tamoxifen and 5-fluorouracil without DNA damage or over similarly treated Cdkn2atm2.1Rdp cells in irradiated chimera experiments
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• administration of tamoxifen prior to 3 weeks of age results in stunted growth
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• administration of tamoxifen prior to 3 weeks of age results in death by 12 weeks of age without tumor formation
|
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• when tamoxifen is administered after 3 weeks of age more tumors form than without tamoxifen
• tumors most often in extremities, rib cage, and facial tissue
• tumors rare in dermis, liver, and bone
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• mice develop clear cell sarcoma mimicking tumors across a broad anatomic distribution at 3-6 months of age in the absence of tamoxifen, indicating leakiness of the cre transgene
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• all mice have tumors by 12 weeks regardless of treatment
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop a tumor within the skull between 3 and 6 months of age; tumors are found primarily in the brain parenchyma, but also in the choroid plexus and orbit
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• tumors show characteristic nests of polygonal cells with an open chromatin pattern, surrounded by neatly arcading capillary and larger vascular channels, resembling alveolar soft part sarcoma
• tumors often arise in or near the leptomeninges, along sulci
• some tumors show aggressive invasive growth, with extensions of tumor cells into the cerebellum, cerebrum, and the vessels of the choroid plexus
• mice do not develop tumors in the skeletal muscle
• tumors form in the areas highest in lactate, the cranial vault, express high levels of lactate importers, have abundant mitochondria, metabolize lactate as a metabolic substrate, and respond to exogenous lactate administration with increased cell proliferation and angiogenesis
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• mice often exhibit enlargement of the occipital bone from the inner soft tissue expansion
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• mice often exhibit enlargement of the occipital bone from the inner soft tissue expansion
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| alveolar soft part sarcoma | DOID:4239 |
OMIM:606243 |
J:217462 | |
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated mice exhibit normal glomerular development
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mouse embryonic fibroblasts exhibit cell cycle arrest after 6 days in culture unlike wild-type cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in MEFs at later time points after OHT treatment and serum addition cells develop large aberrant nuclei with frequent micronuclei
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• in MEFS after OHT treatment and serum addition increases in the population of cells with 4N and 8N DNA content are seen
|
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• live cell imaging indicates a median 8 h delay in mitotic entry in MEFS after OHT treatment and serum addition compared to controls
• in MEFS after OHT treatment and serum addition more cells are in prophase and most of these show an early prophase phenotype
• in MEFS after OHT treatment and serum addition almost no cells in metaphase, anaphase, and telophase are detected
• in MEFS after OHT treatment and serum addition cells in prometaphase have a monopolar spindle with closely adjacent chromosomes, the presence of these monopolar spindles activates the spindle checkpoint
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• in MEFS 28 h after OHT treatment and serum addition the percent of cells positive for PH3 is increased about 3 fold compared to controls
• however, the timing of the peak in PH3 positive cells is similar to controls
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• growth defect in MEFs following OHT treatment and serum addition
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E12.5, following tamoxifen treatment at E8.5, mice display an expansion of the cortical hem and a reduction in dorsal telencephalon
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• at E12.5, following tamoxifen treatment at E8.5, mice display an expansion of the cortical hem and a reduction in dorsal telencephalon
• treatment with tamoxifen at E10.5 results in subtle to inapparent abnormalities in the cortical hem at E12.5
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|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• naive CD4+ T cells release more interferon gamma than controls after cre-mediated deletion of Rnasen induced by tamoxifen treatment
• deficient CD4+ T cells are capable of differentiating into Th1 or Th2 cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after 3 to 4 days in culture tamoxifen-treated mouse embryonic fibroblasts (MEFs) arrest with 2N or 4N DNA content and exhibit reduced S and M phase unlike wild-type MEFs
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• after 3 to 4 days in culture tamoxifen-treated mouse embryonic fibroblasts (MEFs) exhibit a flattened senescence-like morphology unlike wild-type MEFs
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• tamoxifen-treated mouse embryonic fibroblasts exhibit decreased DNA-damage signaling via Trp53, Cdkn1a and Chek1 compared to wild-type cells
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• tamoxifen-treated mouse embryonic fibroblasts exhibit decreased DNA-damage signaling via Trp53, Cdkn1a and Chek1 compared to wild-type cells
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|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following injection of tamoxifen at E10.5 most embryonic cells appear to be in prometaphase
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• following injection of tamoxifen at E10.5 embryos show a 4 fold increase in PH3 positive cells in the thymus and lungs compared to controls
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• following injection of tamoxifen at E10.5 about a 3 fold increase in the percentage of apoptotic cells in the thymus and lungs is seen
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Internal bleeding and anemia, and hemorrhages in the lung and GI tract in tamoxifen treated Acvrl1tm2.1Spo/Acvrl1tm2.1Spo Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+ mice
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• adult mice administered with tamoxifen die 9-21 days after a single injection
• tamoxifen treated females show a shorter survival span than males
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• in tamoxifen treated mutants
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• tamoxifen treated mutants show signs of illness such as slow movements, weight loss, pale paws, and low pO2 levels from 8-10 days after tamoxifen injection
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• pulmonary arteries and veins are dilated
• high vascular permeability
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• uterus shows signs of arteriovenous malformations in tamoxifen treated mutants
• mutants bearing excisional wounds on the dorsal skin and ear and treated with tamoxifen form arteriovenous shunts in the blood vessels near the wounds
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• arteriovenous malformations in the GI tract of tamoxifen treated mutants are located in the Peyer's patches of small intestine and appendix
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• in tamoxifen treated mutants
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• in tamoxifen treated mutants
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• tamoxifen treated mutants show signs of hemorrhages in the lungs
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• arteriovenous malformations in the GI tract of tamoxifen treated mutants are located in the Peyer's patches of small intestine and appendix
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• tamoxifen treated mutants exhibit darkened feces indicative of the presence of blood
|
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• tamoxifen treated mutants exhibit reduced hematocrit
|
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• pulmonary arteries and veins are dilated
• high vascular permeability
|
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• tamoxifen treated mutants show signs of hemorrhages in the lungs
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hereditary hemorrhagic telangiectasia | DOID:1270 |
OMIM:187300 OMIM:600376 OMIM:601101 OMIM:615506 |
J:154620 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• hematopoietic stem and progenitor cells of irradiated mice treated with tamoxifen do not exhibit a selective advantage over cells not expressing the modified cDNA
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• hematopoietic stem and progenitor cells of irradiated mice treated with tamoxifen do not exhibit a selective advantage over cells not expressing the modified cDNA
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most females that develop lymphomas die at about 9 weeks post-4OHT injection
• all mutants die from tumor burden by 45 weeks post-4OHT injection
|
|
• treatment of mice with 4OHT at 6 weeks of age to induce cre-mediated recombination results in tumor formation with a mean latency of 17 weeks
• multiple tumors are seen in 27.3% of 4OHT-treated mice
• 46.1% of females develop endometrial cancer after 4OHT treatment
|
 |
• 35% of males develop intestinal cancer after 4OHT treatment, arising from the colorectum and small intestine
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|
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• 20% of males develop prostate cancer after 4OHT treatment
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|
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• prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment
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• 76.9% incidence of lymphomas in females after 4OHT treatment
• 40% incidence of lymphomas in males after 4OHT treatment
• lymphomas mainly arise from the thymus and mesenteric lymph nodes
• all lymphomas are derived from CD3+ T-cells with either a mature appearance of small lymphocytes or large lymphoblasts
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• about 50% of males and females exhibit malignant tumors at 21 weeks and 10-11 weeks after 4OHT treatment, respectively
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• 10% of males and 15.4% of females develop squamous cell carcinoma of the epidermis after 4OHT treatment
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• males develop small or large intestinal polyps at more than 35 weeks post 4OHT treatment
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• 35% of males develop intestinal cancer after 4OHT treatment, arising from the colorectum and small intestine
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• prostate hyperplasia is observed at 4-6 weeks post 4-OHT treatment
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• 20% of males develop prostate cancer after 4OHT treatment
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• prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment
|
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• 76.9% incidence of lymphomas in females after 4OHT treatment
• 40% incidence of lymphomas in males after 4OHT treatment
• lymphomas mainly arise from the thymus and mesenteric lymph nodes
• all lymphomas are derived from CD3+ T-cells with either a mature appearance of small lymphocytes or large lymphoblasts
|
|
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• prostate hyperplasia is observed at 4-6 weeks post 4-OHT treatment
|
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• 20% of males develop prostate cancer after 4OHT treatment
|
|
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• prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment
|
 |
• most females develop endometrial hyperplasia at between 7 and 9 weeks post 4-OHT treatment
|
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• 10% of males and 15.4% of females develop squamous cell carcinoma of the epidermis after 4OHT treatment
|
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• about 50% of males and females exhibit malignant tumors at 21 weeks and 10-11 weeks after 4OHT treatment, respectively
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice lack normal goblet cells unlike wild-type mice
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice
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• in the small intestine and colon following tamoxifen treatment
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• following tamoxifen treatment, enterocyte proliferation in the small intestine and colon is decreased compared to in wild-type mice
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• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells unlike in wild-type mice
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• 24 hours following tamoxifen treatment, the Paneth cell compartment is expanded compared to in wild-type mice
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice
|
|
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice
|
|
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice
|
|
• 24 hours following tamoxifen treatment, the Paneth cell compartment is expanded compared to in wild-type mice
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice
|
|
• tamoxifen-treated mice lack normal goblet cells unlike wild-type mice
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice
|
|
• in the small intestine and colon following tamoxifen treatment
|
|
• following tamoxifen treatment, enterocyte proliferation in the small intestine and colon is decreased compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after tamoxifen treatment, the external granule cell layer is much thinner than that of control littermates
• after tamoxifen treatment, the layer is depleted of cycling immature precursors
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|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no cycling granule neuron precursor cells are detected in the external granule cell layer 10 days after tamoxifen treatment
|
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• 10 days after tamoxifen treatment
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• 10 days after tamoxifen treatment most mice have atrophic cerebella
|
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• no cycling granule neuron precursor cells are detected in the external granule cell layer 10 days after tamoxifen treatment
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• ectopic masses show numerous mitotic granule neuron precursors 10 days after tamoxifen treatment
|
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• 10 days after tamoxifen treatment, neoplastic and preneoplastic lesions in which the external granule layer lacks the normal layered structure develop in the external layer of the cerebellum
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• hypertrophic 10 days after tamoxifen treatment
|
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• 10 days after tamoxifen treatment, neoplastic and preneoplastic lesions in which the external granule layer lacks the normal layered structure develop in the external layer of the cerebellum
|
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• ectopic masses show numerous mitotic granule neuron precursors 10 days after tamoxifen treatment
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|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• GFP+ hematopoietic stem and progenitor cells (HSPC) from irradiated mice transplanted into irradiated mice reconstitute the HSPC population exhibit a competitive advantage over HSPC from untreated mice compared with cells from similarly irradiated wild-type mice
|
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following treatment with tamoxifen, cultured tracheal ciliated epithelium exhibits no ciliary activity likely due to a lack of outer dynein arms unlike similarly treated wild-type samples
• however, epithelium morphology and number of ciliated cells are normal following treatment with tamoxifen
|
|
• tamoxifen-treated mice exhibit chronic rhinosinusitis unlike wild-type mice
• however, no lung inflammation develops in tamoxifen-treated mice
|
|
• after 3 months, tamoxifen-treated mice exhibit absent mucociliary clearance in the nasopharynx and a 50% decreased in the trachea compared with wild-type mice
• after 6 months, 3 of 4 tamoxifen-treated mice exhibit no mucociliary clearance in the trachea while 1 of 4 mice exhibit a substantial reduction in clearance compared with similarly treated wild-type mice
• after 7.5 months, tamoxifen-treated mice exhibit no mucociliary clearance in the trachea compared with similarly treated wild-type mice
|
|
• tamoxifen-treated mice exhibit chronic rhinosinusitis unlike wild-type mice
• however, no lung inflammation develops in tamoxifen-treated mice
|
| N |
• despite ciliary defects, tamoxifen-treated mice exhibit no evidence hydroencephaly
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| primary ciliary dyskinesia 1 | DOID:0110594 |
OMIM:244400 |
J:155730 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 6 months after tamoxifen treatment, mice develop intestinal disease and eventually die or are sacrificed
|
|
• tamoxifen-treated mice exhibit partial or complete fibrosis of the small intestine and cecum unlike in wild-type mice with increased submucosal connective tissue and proportional increase in fibroblast-like cells and collagenous matrix
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• tamoxifen-treated mice exhibit partial or complete fibrosis of the small intestine and cecum unlike in wild-type mice with increased submucosal connective tissue and proportional increase in fibroblast-like cells and collagenous matrix
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• tamoxifen-treated mice exhibit partial or complete fibrosis of the small intestine and cecum unlike in wild-type mice with increased submucosal connective tissue and proportional increase in fibroblast-like cells and collagenous matrix
|
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• in tamoxifen-treated mice
|
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• in tamoxifen-treated mice
|
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• sclerotic glomeruli in tamoxifen-treated mice
|
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• in tamoxifen-treated mice
|
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• enlarged glomeruli in tamoxifen-treated mice
|
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• in tamoxifen-treated mice
|
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• at between 44 and 76 weeks of age, 5 of 29 tamoxifen-treated mice develop sarcomas arising from dermis or muscle connective tissue
|
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• in tamoxifen-treated mice
|
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• around the bronchioles in tamoxifen-treated mice
|
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• in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all tamoxifen-treated mice develop sarcomas of the skin or muscle connective tissue after 10 to 19 weeks
|
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• 2 tamoxifen-treated mice develop large intestinal tumors resembling undifferentiated fibrosarcomas
|
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• tamoxifen-treated mice develop muscle fibrosis at 10 to 19 weeks of age
|
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• tamoxifen-treated mice develop skin fibrosis at 10 to 19 weeks of age
|
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• after 15 weeks, tamoxifen-treated mice exhibit intestinal fibrosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• during the initial 3 days after cre induction by tamoxifen, all mice show decrease in body weight due to decreased food intake, but whereas controls regain recover some weight, experimental mice do not
|
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• following cre induction, animals exhibit a decreased respiratory exchange ratio (RER) indicative of pure fat oxidation compared to controls by day 6
|
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• inspection of animals dying after cre induction by tamoxifen shows loss of body fat in these mice
• analyses of carcasses show significant decreases in whole body fat mass, but not lean mass
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when cre expression is induced with a tamoxifen-containing diet (400 mg/kg of chow), mice die by day 9 post-introduction of tamoxifen
|
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• during the initial 3 days after cre induction by tamoxifen, all mice show decrease in body weight due to decreased food intake, but whereas controls regain recover some weight, experimental mice do not
|
|
• mice show a cumulative loss of body weight compared to controls following cre induction, but energy intake (cumulative food intake) is similar to controls
|
| N |
• without induction of cre by tamoxifen treatment, animals are indistinguishable from controls
|
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• increased fat oxidation after induction is basis for increased weight loss
|
|
• following cre induction, animals exhibit a decreased respiratory exchange ratio (RER) indicative of pure fat oxidation compared to controls by day 6
|
|
• inspection of animals dying after cre induction by tamoxifen shows loss of body fat in these mice
• analyses of carcasses show significant decreases in whole body fat mass, but not lean mass
|
|
• increased fat oxidation after induction is basis for increased weight loss
|
|
• energy intake on day 7 is significantly higher than on day 1 after cre induction
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice display signs of illness in 3-4 days after the first tamoxifen injection which includes slow movement
|
|
• adults injected with tamoxifen for 3 days develop arteriovenous malformations in AAV-VEGF-induced brain angiogenic foci 8 weeks after induction, with lesions consisting of enlarged vessels
(J:212952)
• tamoxifen treated adults develop arteriovenous malformations around the ear-tag wound
(J:212952)
• areas of wounds in mid-dorsum and ear of tamoxifen-injected mice show the presence of arteriovenous (AV) shunts
(J:227170)
|
|
• macrophages and microhemorrhage are seen around dysplastic vessels of AAV-VEGF injected, tamoxifen treated mice in the brain
|
|
• tamoxifen treated adults develop arteriovenous malformations around the ear-tag wound
(J:212952)
• areas of wounds in mid-dorsum and ear of tamoxifen-injected mice show dilated and torturous vessels and the presence of arteriovenous (AV) shunts
(J:227170)
• however, blood vessels away from the wound have normal morphology
(J:227170)
|
|
• mice display signs of illness in 3-4 days after the first tamoxifen injection which includes diarrhea
|
|
• tamoxifen treated adults develop arteriovenous malformations around the ear-tag wound
(J:212952)
• areas of wounds in mid-dorsum and ear of tamoxifen-injected mice show dilated and torturous vessels and the presence of arteriovenous (AV) shunts
(J:227170)
• however, blood vessels away from the wound have normal morphology
(J:227170)
|
|
• mice display signs of illness in 3-4 days after the first tamoxifen injection which includes dehydration
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hereditary hemorrhagic telangiectasia | DOID:1270 |
OMIM:187300 OMIM:600376 OMIM:601101 OMIM:615506 |
J:212952 , J:227170 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen treated MEFs exhibit disruption of nucleolar structure characteristic of nucleolar stress
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pups from nursing mothers that were injected with tamoxifen to induce Pkd1 deletion in pups, show an increase in the ratio of percent kidney weight to body weight at P23
|
|
• pups from nursing mothers that were injected with tamoxifen to induce Pkd1 deletion in pups, show an increase in the ratio of percent kidney weight to body weight at P23
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice show a very large increase in plasma desmosterol level
• liver, brain, and heart tissue desmosterol levels are elevated in tamoxifen-treated mice
• however, liver, brain and heart tissue cholesterol levels in tamoxifen-treated mice are normal
|
|
• mice treated with tamoxifen at 4-5 weeks of age show an early decline and stable decrease in plasma cholesterol
• however, cholesterol content of liver, brain, and heart is normal
|
|
• bile shows elevated desmosterol levels in tamoxifen-treated mice
• tamoxifen-treated mice show lower biliary cholesterol level
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most mice die soon after birth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mouse embryonic fibroblasts increased expression of VL30-pro endogenous retroviruses (ERV) elements compared with control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• vascular malformations are seen in lymph nodes, spleen, and/or other locations in mice from pregnant females treated with tamoxifen at E5.5
• visible vascular malformations appear as dark, blood-filled, often multi-lobulated cystic masses
• vascular malformations are characterized as venous-capillary mixed-type malformations with ectatic channels and often containing a lymphatic component and no atypia
• numerous, variably-sized, thin-walled ectatic vessels, often separated by increased stroma are seen in these lesion
|
|
• biliary cysts are the most frequent type of cyst seen in mice from pregnant females treated with tamoxifen at E5.5
|
|
• biliary ductule ectasia is seen in some mice treated with tamoxifen at E5.5
|
|
• mammary changes in mice treated with tamoxifen at E5.5 include ductal ectasia
|
|
• seen in some mice treated with tamoxifen at E5.5
|
|
• mammary changes in mice treated with tamoxifen at E5.5 include expansion of the supporting stroma
|
|
• overgrowth of breast tissue is seen in mice from pregnant females treated with tamoxifen at E5.5
|
|
• mammary changes in mice treated with tamoxifen at E5.5 include ductal ectasia
|
|
• seen in some mice treated with tamoxifen at E5.5
|
|
• mammary changes in mice treated with tamoxifen at E5.5 include expansion of the supporting stroma
|
|
• overgrowth of breast tissue is seen in mice from pregnant females treated with tamoxifen at E5.5
|
|
• biliary cysts are the most frequent type of cyst seen in mice from pregnant females treated with tamoxifen at E5.5
|
|
• biliary ductule ectasia is seen in some mice treated with tamoxifen at E5.5
|
|
• biliary cysts are the most frequent type of cyst seen in mice from pregnant females treated with tamoxifen at E5.5
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Proteus syndrome | DOID:13482 |
OMIM:176920 |
J:293971 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice die within 2 weeks of the 4th injection of tamoxifen (4 injections administered over an 8 day period)
|
|
• starting after 3 injections of tamoxifen in mice at 6 - 9 months of age
• becomes significant 1 week after the 4th injection of tamoxifen
|
|
• 1 week after the last tamoxifen injection
|
|
• enhanced lipid peroxidation and impaired electron transport chain activity and ATP production in mitochondria 1 week after the last tamoxifen injection
|
|
• elevated astrocyte activation in the hippocampal region 1 week after the last tamoxifen injection
|
|
• in the hippocampal region 1 week after the last tamoxifen injection
|
|
• 1 week after the last tamoxifen injection
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice treated with tamoxifen after neurogenesis (at E10.5) exhibit normal motor pool formation
|
|
• mice treated with tamoxifen at E8.5 exhibit delayed motor neuron formation compared with control mice
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• at E12.5, mice treated with tamoxifen at E8.5 exhibit fewer Isl1/2+ and vasti, adductor longus and magnus, and posterior gracilis muscle motor neurons compared with control mice
• at E14.5, mice treated with tamoxifen at E8.5 exhibit fewer Isl1/2+ and vasti muscle motor neurons compared with control mice
• however, motor neurons in adductor longus and magnus and posterior gracilis muscles recover by E14.5
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• mice treated with tamoxifen at E8.5 exhibit delayed motor neuron formation compared with control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• inferior fusion defects resulting in notching of the inferior portion
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• rare but consistent phenotype
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E18.5 in mice treated with tamoxifen at E12.5 or E13.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• an increase in cell proliferation is seen in kidney tubules of 6-week old offspring from pregnant females injected with tamoxifen at E17.5
• from P15 to P20, an increase in cell proliferation in the renal medulla is seen the offspring of females injected with tamoxifen at E17.5
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• levels of cAMP are higher in cystic kidneys of the offspring of E17.5 pregnant females injected with tamoxifen
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• kidney primary cilia are stunted and show accumulation of IFT88 protein in bulb-like structures at the distal tips in the offspring of E17.5 pregnant females injected with tamoxifen
• from P15 to P20, an increase in cell proliferation in the renal medulla is seen the offspring of females injected with tamoxifen at E17.5
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• when E17.5 pregnant females are injected intraperitoneally with tamoxifen to induce ubiquitous deletion of Ttc21b, the 6 week old offspring develop cystic kidney disease
• cysts seen in the offspring of E17.5 pregnant females injected with tamoxifen originate from proximal tubules, loops of Henle, and collecting ducts
• 5 week old mice injected intraperitoneally with tamoxifen do not develop kidney cysts after 3 months
• kidneys from offspring of E17.5 pregnant females grown in culture in the presence of 8-bromo-cAMP exhibit increased cystogenic potential and treatment of these cultures with Gant61, a small molecule GLI antagonist, or Sant2, a small molecule SMO antagonist, inhibitors reduces cystogenic potential
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• elevation in ratio of percent kidney weight to body weight is seen in the offspring of E17.5 pregnant females injected with tamoxifen
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• dilations of loops of Henle in the kidney cortex are seen by P15 in the offspring of pregnant females injected with tamoxifen at E17.5
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• dilations of proximal tubules in the kidney cortex are seen by P15 in the offspring of pregnant females injected with tamoxifen at E17.5
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• increase in BUN levels is seen in the offspring of E17.5 pregnant females injected with tamoxifen
|
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• kidney primary cilia are stunted and show accumulation of IFT88 protein in bulb-like structures at the distal tips in the offspring of E17.5 pregnant females injected with tamoxifen
• from P15 to P20, an increase in cell proliferation in the renal medulla is seen the offspring of females injected with tamoxifen at E17.5
|
|
• an increase in cell proliferation is seen in kidney tubules of 6-week old offspring from pregnant females injected with tamoxifen at E17.5
• from P15 to P20, an increase in cell proliferation in the renal medulla is seen the offspring of females injected with tamoxifen at E17.5
|
|
• when E17.5 pregnant females are injected intraperitoneally with tamoxifen to induce ubiquitous deletion of Ttc21b, the 6 week old offspring develop cystic kidney disease
• cysts seen in the offspring of E17.5 pregnant females injected with tamoxifen originate from proximal tubules, loops of Henle, and collecting ducts
• 5 week old mice injected intraperitoneally with tamoxifen do not develop kidney cysts after 3 months
• kidneys from offspring of E17.5 pregnant females grown in culture in the presence of 8-bromo-cAMP exhibit increased cystogenic potential and treatment of these cultures with Gant61, a small molecule GLI antagonist, or Sant2, a small molecule SMO antagonist, inhibitors reduces cystogenic potential
|
|
• elevation in ratio of percent kidney weight to body weight is seen in the offspring of E17.5 pregnant females injected with tamoxifen
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| cystic kidney disease | DOID:2975 | J:213263 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• PFN in adults displays nearly complete loss of alkaline phosphatase expressing Fzd5-null neurons by 10 days after 4HT injection and cre activation, but no loss is observed in Fzd5tm2Nat/+, cre-positive control PFNs 8 days after 4HT treatment
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 4 of 9 tamoxifen-treated mice exhibit intestinal fibrosis
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• in one tamoxifen-treated mouse
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• sclerotic glomeruli in tamoxifen-treated mice
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• enlarged glomeruli in tamoxifen-treated mice
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• in tamoxifen-treated mice
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• in tamoxifen-treated mice
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• in some tamoxifen-treated mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the spleen and bone marrow B cell subsets of tamoxifen-treated mice
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• tamoxifen-treated B cell precursors fail to exhibit an increase in bafilomycin-induced autophagy unlike in control cells
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• in the spleen and bone marrow B cell subsets of tamoxifen-treated mice
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• tamoxifen-treated B cell precursors fail to exhibit an increase in bafilomycin-induced autophagy unlike in control cells
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|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tamoxifen-treatment, mouse embryonic fibroblasts (MEFs) exhibit random migration in response to an HMGB1 gradient unlike wild-type cells
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• 30 to 60 minutes after exposure to HMGB1, tamoxifen-treated MEFs exhibit reduced migration velocity compared with wild-type mice
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• following tamoxifen-treatment, MEFs exhibit impaired chemotaxis in response to HMGB1 compared with wild-type cells
• however, chemotaxis in response to PDGF is normal and chemotaxis is rescued by over expression of Nfkb2
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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 04/16/2024 MGI 6.23 |
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