Analysis Tools|
Allele Symbol Allele Name Allele ID |
Ptentm2Mak targeted mutation 2, Tak W Mak MGI:2182005 |
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| Summary |
36 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• astrocytes transfected with a cre-expresing adenovirus exhibit increased mTor signaling-dependent proliferation compared to in control cells
• however, proliferation can be reduced by rapamycin treatment
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• ~10% of mice treated with doxycycline in utero (E10-E16) survive to adulthood but develop spontaneous lung tumors, not observed in wild-type controls during a 90-wk observation period
• the cancer-free survival rates for prenatally doxycycline-treated mice are significantly lower than for controls
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• ~90% of mice treated with doxycycline in utero (E10-E16) die within 2 hrs of birth due to respiratory failure
• in contrast, mice treated with doxycycline postnatally (P21-P27 or P84-P90) do not show any neonatal lethality
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• neonates treated with doxycycline in utero (E10-E16) display a cyanotic skin color
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• neonates treated with doxycycline in utero (E10-E16) display significant hypoxia
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• neonates treated with doxycycline in utero (E10-E16) display respiratory acidosis
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• following urethane treatment, 94% (17 of 18) of mice treated with doxycycline in utero (E10-E16) developed lung tumors (one lung adenocarcinoma, the rest being lung adenomas) relative to only 42% (11 of 26) of wild-type controls (all lung adenomas); also seen in mice treated with doxycycline postnatally (P21-P27)
• both prenatal and postnatal doxycycline treatment resulted in significantly increased numbers and sizes of urethane-induced lung tumors relative to those seen in wild-type controls
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• at birth, mice treated with doxycycline in utero (E10-E16) show a 1.5-fold increase in total lung cell numbers relative to controls
• at E19.5, the numbers of both alveolar epithelial cells and mesenchymal cells are significantly increased due to enhanced cell proliferation rather than reduced apoptosis
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• neonates treated with doxycycline in utero (E10-E16) display respiratory acidosis
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• 13 of 14 mice treated with doxycycline in utero (E10-E16) developed lung adenocarcinomas, not observed in any wild-type controls during a 90-wk observation period
• 13 of 15 (87%) of mice treated with doxycycline postnatally (P21-P27) developed spontaneous lung adenocarcinomas, not observed in any wild-type controls during the 40- to 70-wk observation period
• notably, Kras was mutated in 33% of spontaneous lung adenocarcinomas observed in P21-P27 doxycycline treated mice
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• 1 of 14 mice treated with doxycycline in utero (E10-E16) developed a lung squamous cell carcinoma
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• mice treated with doxycycline in utero (E10-E16) display delayed lung development at the terminal sac stage (E17.5 to P0) relative to control mice
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• at E19.5, mice treated with doxycycline in utero (E10-E16) show an expanded mesenchymal cell population, due to increased numbers of myofibroblast precursors in the septa
• mesenchymal cell numbers are significantly increased due to enhanced cell proliferation rather than reduced apoptosis
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• at the terminal sac stage (E17.5 to P0), mice treated with doxycycline in utero (E10-E16) display fewer saccular structures with a significant delay in the dilatation of the distal tubules relative to control mice
• at birth, mice treated with doxycycline in utero (E10-E16) display septal hyperplasia with increased mesenchymal cells and reduced airspaces relative to controls
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• at birth, mice treated with doxycycline in utero (E10-E16) display reduced airspaces relative to controls
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• at 8 weeks of age, mice treated with doxycycline postnatally (P21-P27) show a 5.2-fold increase in BASCs and a 4.0-fold increase in side population cells relative to wild-type controls; similar increases are observed in E10-E16 doxycycline treated mice
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• neonates treated with doxycycline in utero (E10-E16) display significant bronchiolar epithelial hyperplasia relative to controls
• mice treated with doxycycline postnatally (P21-P27 or P84-P90) display mild bronchiolar epithelial hyperplasia relative to controls; however no significant differences in bronchiolar epithelial differentiation are observed
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• at E19.5, mice treated with doxycycline in utero (E10-E16) display increased numbers of undifferentiated cuboidal alveolar epithelial cells of enlarged size relative to controls
• mice treated with doxycycline postnatally (P21-P27 or P84-P90) display mild alveolar epithelial hyperplasia and increased cell size of alveolar epithelial cells relative to controls; however, no significant differences in alveolar epithelial differentiation are observed
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• at E19.5, mice treated with doxycycline in utero (E10-E16) display impaired type I cell differentiation, as shown by severely reduced aquaporin-5 (AQP5) immunostaining relative to controls
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• at E19.5, mice treated with doxycycline in utero (E10-E16) display immature rounded to cuboidal cells with poorly differentiated cytoplasm, rare apical microvilli, few lamellar bodies, and severely reduced SP-C immunostaining relative to control mice
• at P0, mice treated with doxycycline in utero (E10-E16) also display PAS positivity unlike wild-type control mice
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• at E19.5, mice treated with doxycycline in utero (E10-E16) display fewer lamellar bodies than control mice
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• at E19.5, mice treated with doxycycline in utero (E10-E16) display a much thicker blood-air barrier than control mice
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• neonates treated with doxycycline in utero (E10-E16) display irregular breathing and gasping
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• ~90% of mice treated with doxycycline in utero (E10-E16) die of respiratory failure
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• at E19.5, mice treated with doxycycline in utero (E10-E16) display a significant reduction in the expression levels of surfactant proteins A (SP-A), SP-B, SP-C and SP-D relative to control mice
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• following urethane treatment, 94% (17 of 18) of mice treated with doxycycline in utero (E10-E16) developed lung tumors (one lung adenocarcinoma, the rest being lung adenomas) relative to only 42% (11 of 26) of wild-type controls (all lung adenomas); also seen in mice treated with doxycycline postnatally (P21-P27)
• both prenatal and postnatal doxycycline treatment resulted in significantly increased numbers and sizes of urethane-induced lung tumors relative to those seen in wild-type controls
|
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• 13 of 14 mice treated with doxycycline in utero (E10-E16) developed lung adenocarcinomas, not observed in any wild-type controls during a 90-wk observation period
• 13 of 15 (87%) of mice treated with doxycycline postnatally (P21-P27) developed spontaneous lung adenocarcinomas, not observed in any wild-type controls during the 40- to 70-wk observation period
• notably, Kras was mutated in 33% of spontaneous lung adenocarcinomas observed in P21-P27 doxycycline treated mice
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• 1 of 14 mice treated with doxycycline in utero (E10-E16) developed a lung squamous cell carcinoma
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• at E19.5, mice treated with doxycycline in utero (E10-E16) show an expanded mesenchymal cell population, due to increased numbers of myofibroblast precursors in the septa
• mesenchymal cell numbers are significantly increased due to enhanced cell proliferation rather than reduced apoptosis
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• at birth, mice treated with doxycycline in utero (E10-E16) show a 1.5-fold increase in total lung cell numbers relative to controls
• at E19.5, the numbers of both alveolar epithelial cells and mesenchymal cells are significantly increased due to enhanced cell proliferation rather than reduced apoptosis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice injected with tamoxifen at P0 and P1 have a median survival of 153 days
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• mice injected with tamoxifen at P0 and P1 begin to exhibit increasing macrocephaly at 2-3 months of age
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• mice injected with tamoxifen at P0 and P1 begin to exhibit lethargy at 2-3 months of age
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• mice injected with tamoxifen at P0 and P1 exhibit ataxia beginning at 2-3 months of age
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• mice injected with tamoxifen at P0 and P1 exhibit seizures beginning at 2-3 months of age
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• brains of mice treated with tamoxifen at birth show hydrocephalus
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• brains of mice treated with tamoxifen at birth show dramatic increase in overall size, especially the cerebellum
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• organization of cell layers of the cerebellum are disrupted in mice treated with tamoxifen at birth
• cerebellum hypertrophy in mice treated with tamoxifen at birth
• cerebellum shows multiple perivascular proliferative niches in mice treated with tamoxifen at birth, composed of hyperchromatic cells with progenitor-like morphology
• the perivascular hyperplastic lesions vary in size and are seen as early as 3 months of age, they grow surrounding CD34+ blood vessels and have a high percentage of Ki67+ cells
• lesions occur more frequently in anterior and lateral cerebellar lobules and in areas around the pia between lobules
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• Purkinje cells are not well aligned at the interface of the internal granule layer and molecular layer in mice treated with tamoxifen at birth
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• size of granule cells is larger in aging mice that were treated with tamoxifen at birth
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• molecular layer is thickened with ectopic granule cells in mice treated with tamoxifen at birth
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• the internal granule layer is thinner in mice treated with tamoxifen at birth
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• molecular layer is thickened with ectopic granule cells in mice treated with tamoxifen at birth
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• mice injected with tamoxifen at P0 and P1 begin to exhibit progressive neurologic abnormalities at 2-3 months of age
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• mice injected with tamoxifen at P0 and P1 exhibit seizures beginning at 2-3 months of age
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| N |
• perivascular hyperplastic lesions in the cerebellum persist but do not develop into tumors up to 10 months of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Cowden syndrome | DOID:6457 |
OMIM:PS158350 |
J:237990 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• all die by 29 weeks of age, with an average of 10 weeks
(J:75500)
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• 11 of 25 develop seizures by 9 weeks of age; symptoms include episodes of front-paw tremors followed by spasms of hind legs
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• beyond 6 weeks, mice exhibit epileptiform activity associated with tonic-clonic seizures
• mice exhibit subclinical electrographic seizures lasting for at least 10 seconds largely without obvious behavioral changes unlike in wild-type mice
• at 6 weeks, two of seven mice display behavioral changes characteristic of tonic-clonic activity
• at 9 weeks, three of seven mice display behavioral changes characteristic of tonic-clonic activity
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• mice exhibit isolated interictal spikes, short trains of repetitive spike lasting less than 5 seconds and long runs of repetitive spikes lasting between 5 and 10 seconds
• spike waves are more frequent at 9 weeks than at 6 weeks
• however, treatment with rapamycin reduces the severity of electrographic abnormalities
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• often see hydrocephalus of the lateral ventricles
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• 43% increased in brain size at 10-14 weeks of age, but not at 4 weeks
(J:75500)
• variable with apparent enlargement of cortical, hippocampal and cerebellar structures
(J:149829)
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• prominent astrogliosis in the hippocampus and the sub-pial surface
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• disorganization of the dentate gyrus at 10 weeks of age, characterized by marked undulation of the granule-cell layer
• intercellular spaces between granule-cell bodies, containing thick neuronal dendrites and astrocytes are expanded
• granule cells of the dentate gyrus have a greater surface area (are enlarged)
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• sclerosis of the pyramidal cell layer of the CA3
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• reduction in pyramidal cell density of the cornu ammonis
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• enlarged cerebellum
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• thickened cerebellar folia
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• multifocal persistence of the external granular cell layer at the pial surface
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• those Purkinje cells remaining are atrophic or dysplastic as indicated by dendritic coarsening and axonal swelling
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• partial loss of Purkinje cells
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• soma size is increased in granule neurons at 10 weeks of age
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• mutants exhibit heterotopic neuronal clusters scattered in the molecular layer
• the molecular layer is thickened, especially at sites of heterotopic lesions
• disorganization, dysplasia, gliosis and elevated myelination in the molecular layer
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• gliosis in the molecular layer
• astrogliosis is visible in close proximity to the affected heterotopic neurons in the cerebellum and in the hippocampus and the sub-pial surface
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• cortical Pten-negative neurons are hypertrophic
• at P12, soma size of Pten-negative neurons is increased 1.7-fold compared with wild-type neurons
• adult Pten-negative neurons are larger than in wild-type mice
• however, Pten-negative pyramidal neurons do not exhibit an increase in size with age and treatment with rapamycin suppresses neuron hypertrophy
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• 11 of 25 develop seizures by 9 weeks of age; symptoms include episodes of front-paw tremors followed by spasms of hind legs
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• beyond 6 weeks, mice exhibit epileptiform activity associated with tonic-clonic seizures
• mice exhibit subclinical electrographic seizures lasting for at least 10 seconds largely without obvious behavioral changes unlike in wild-type mice
• at 6 weeks, two of seven mice display behavioral changes characteristic of tonic-clonic activity
• at 9 weeks, three of seven mice display behavioral changes characteristic of tonic-clonic activity
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• mice exhibit isolated interictal spikes, short trains of repetitive spike lasting less than 5 seconds and long runs of repetitive spikes lasting between 5 and 10 seconds
• spike waves are more frequent at 9 weeks than at 6 weeks
• however, treatment with rapamycin reduces the severity of electrographic abnormalities
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• brain lesions are categorized as hamartomas
• however, do not develop glioblastomas between 4-19 weeks of age
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• variable with apparent enlargement of cortical, hippocampal and cerebellar structures
(J:149829)
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| brain disease | DOID:936 | J:149829 | ||
| Cowden syndrome | DOID:6457 |
OMIM:PS158350 |
J:75500 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• death before 18 months from progressive hind limb paralysis
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• bodies longer than controls at birth
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• width of long bones is noticeably greater
• lengths of tibia and femur are normal at 50 days of age
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• 14 cartilaginous nodules in epiphyseal cavities of femurs from 9 mice
• clusters of nonproliferating chondrocytes appear in the central regions of growth plates at 3 days of age
• accelerated proliferation of flat shaped peripheral chondrocytes
• some smaller lower zone chondrocytes recover proliferative ability
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• four cartilaginous nodules in the bone marrow cavity of tibias and femora of four mice
• cartilaginous nodules found in close proximity to the metaphyseal growth plates of knee joints
• non hypertrophic cartilagenous clusters penetrating the bone marrow cavity become hypertrophic
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• cartilaginous nodules limited at the periphery by lamellae of well mineralized trabecular bone
• nodules disappear after fusion of growth plates at 6 months
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• neoplastic cores are hypocellular with enlarged balloon-like chondrocytes
• chondrocytes within neoplastic cores are surrounded by fewer collagen fibers
• have a distended and fragmented endoplastic reticulum
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• cartilaginous nodules in bone marrow cavity
• cartilaginous nodules in epiphyseal cavities
• non hypertrophic cartilagenous clusters penetrating the bone marrow cavity become hypertrophic and gradually form pseudogrowth plates
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• growth plates are essentially normal embryonically
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• neoplastic clusters penetrate through the hypertrophic zone into the bone marrow cavity
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• clusters of "resting" chondrocytes develop into neoplastic cores by day 5
• clusters become more distinct by day 7 and migrate toward epiphyses
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• progressive hind limb paralysis results in death by 18 months
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• a sharp decline in survival is noted after P15
• none of the mice survive beyond 26 days of life
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• at 2 wks of age, mice are readily identified by their smaller body size and sickly appearance
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• neonatal kidneys display kinked collecting ducts
• DBA staining of collecting tubules within the cortex indicates higher density and cystic morphology
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• at P14, the density of glomeruli within the outermost cortical layer is significantly increased
• at P14, most glomeruli are small and unevenly positioned within the cortex (i.e. subcapsular)
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• at P14, aberrant subcapsular glomeruli show little evidence of capillary blood flow
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• in vitro, E11.5 kidneys cultured for 48 hrs in serum free media display subtle branching defects including asymmetric ureteric bud tips that are often dilated, abnormally enlarged misshapen ampullae, discontinuous and jagged laminin basement membranes, kinked ureteric bud stalks and small ectopic bud outgrowths
• neonatal kidneys exhibit terminal end buds that are often dilated and connected to misshaped stalks
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• in vitro, E11.5 kidneys cultured for 48 hrs in serum free media display small ectopic bud outgrowths
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• at P14, aberrant subcapsular glomeruli show little evidence of capillary blood flow
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• hyperplastic outer root sheaths are seen at 3 months of age
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• observed at 3 months of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 100% of mice induced with tamoxifen at P0 and P1 develop medulloblastoma with a median onset of morbidity of 63 days of age
• medullablastomas of tamoxifen treated mice show extensive and abnormal vascularization and highly differentiated tumor cells surrounding a perivascular tumor stem cell niche that is not seen in single Trp53 conditional mutants
• blood clots are often seen in the lumen of abnormal blood vessels
• medulloblastoma initiates from a perivascular tumor stem cell niche
• medulloblastomas of tamoxifen treated mice acquire somatic inactivation of Ptch1 and show expression signatures of sonic hedgehog subgroup medulloblastoma
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• 18 of 26 mice treated with tamoxifen at P0 and P1 develop gliomas in the forebrain and brain stem
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• 100% of mice induced with tamoxifen at P0 and P1 develop medulloblastoma with a median onset of morbidity of 63 days of age
• medullablastomas of tamoxifen treated mice show extensive and abnormal vascularization and highly differentiated tumor cells surrounding a perivascular tumor stem cell niche that is not seen in single Trp53 conditional mutants
• blood clots are often seen in the lumen of abnormal blood vessels
• medulloblastoma initiates from a perivascular tumor stem cell niche
• medulloblastomas of tamoxifen treated mice acquire somatic inactivation of Ptch1 and show expression signatures of sonic hedgehog subgroup medulloblastoma
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• 18 of 26 mice treated with tamoxifen at P0 and P1 develop gliomas in the forebrain and brain stem
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• cerebellum at P21 of mice treated with tamoxifen at birth shows disrupted lamination and abundant Ki67+ proliferative cells throughout the cerebellum , which are concentrated around blood vessels either under the pial surface or in the parenchyma
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| medulloblastoma | DOID:0050902 |
OMIM:155255 |
J:237990 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice injected with tamoxifen at P10 develop liver tumors that are exclusively intrahepatic cholangiocarcinoma
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• mice injected with tamoxifen at 8 weeks after birth develop multiple liver tumors that are all hepatocellular carcinoma and hepatocellular dysplasia, but not intrahepatic cholangiocarcinoma
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• mice injected with tamoxifen at P10 develop liver tumors that are exclusively intrahepatic cholangiocarcinoma
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• mice injected with tamoxifen at 8 weeks after birth develop multiple liver tumors that are all hepatocellular carcinoma and hepatocellular dysplasia, but not intrahepatic cholangiocarcinoma
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• mice injected with tamoxifen at P10 develop liver tumors that are exclusively intrahepatic cholangiocarcinoma
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice administered tamoxifen at 8 weeks of age show a median survival of 30 days after tamoxifen injection
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• colonic serrated epithelial changes in tamoxifen treated mice
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• hyperplastic changes of gastric mucosa in tamoxifen treated mice
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• extrahepatic bile duct is rigid and dilated in tamoxifen treated mice
• papillary hyperplasia of the extrahepatic biliary tract
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• papillary hyperplasia of the gallbladder in tamoxifen treated mice
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• gallbladder and cystic duct are rigid and dilated in tamoxifen treated mice
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• in tamoxifen treated mice
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• PanIN-like lesions and hyperplasia in the pancreatic ducts in tamoxifen treated mice
• however, no obvious tumors are seen in mice administered tamoxifen at 8 weeks of age
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• obstructive pneumonia in tamoxifen treated mice
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• extrahepatic bile duct is rigid and dilated in tamoxifen treated mice
• papillary hyperplasia of the extrahepatic biliary tract
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• papillary hyperplasia of the gallbladder in tamoxifen treated mice
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• gallbladder and cystic duct are rigid and dilated in tamoxifen treated mice
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• in tamoxifen treated mice
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• liver of tamoxifen treated mice shows pre-malignant papillary ductal lesions in periportal areas
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• PanIN-like lesions and hyperplasia in the pancreatic ducts in tamoxifen treated mice
• however, no obvious tumors are seen in mice administered tamoxifen at 8 weeks of age
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• obstructive pneumonia in tamoxifen treated mice
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• papillary hyperplasia of bronchial epithelia in tamoxifen treated mice
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• respiratory failure by lung lesions in tamoxifen treated mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tamoxifen- and beta-naphthoflavone-induced mice median survival is 99 days compared to 405 days for wild-type Pten homozygotes or 409 days for wild-type Apc homozygotes
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• 95% of tamoxifen- and beta-naphthoflavone-induced mice exhibit large, flattened, ulcerated lesions in the small intestine unlike control mice homozygous for either a wild-type Pten or Apc allele
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• tamoxifen- and beta-naphthoflavone-induced mice develop invasive adenocarcinomas in the small intestines with luminal ulceration, and both acute and chronic inflammation compared to control mice that exhibit begnin neoplasms
• invasion and destruction of the small intestinal wall and peritoneal serosa results in localized peritonitis in tamoxifen- and beta-naphthoflavone-induced mice
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• invasion and destruction of the small intestinal wall and peritoneal serosa by adenocarcinomas results in localized peritonitis in tamoxifen- and beta-naphthoflavone-induced mice
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• tamoxifen- and beta-naphthoflavone-induced mice develop invasive adenocarcinomas in the small intestines with luminal ulceration, and both acute and chronic inflammation compared to control mice that exhibit begnin neoplasms
• invasion and destruction of the small intestinal wall and peritoneal serosa results in localized peritonitis in tamoxifen- and beta-naphthoflavone-induced mice
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• invasion and destruction of the small intestinal wall and peritoneal serosa by adenocarcinomas results in localized peritonitis in tamoxifen- and beta-naphthoflavone-induced mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• some lesions are diagnosed as intrahepatic cholangiocarcinoma by the appearance of adenocarcinoma showing tubular and/or papillary structures with a fibrous stroma; these tumor cells show loss of Pten expression
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• mice develop liver tumors at 6 months of age, showing obvious symptoms after 7 months with abdominal distension due to multiple tumors at later stages
• mice develop liver tumors with both hepatocyte and cholangiocyte differentiation
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• majority of large nodules are hepatocellular dysplasia, a precursor lesion of hepatocellular carcinoma
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• some lesions are diagnosed as intrahepatic cholangiocarcinoma by the appearance of adenocarcinoma showing tubular and/or papillary structures with a fibrous stroma; these tumor cells show loss of Pten expression
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• mice develop liver tumors at 6 months of age, showing obvious symptoms after 7 months with abdominal distension due to multiple tumors at later stages
• mice develop liver tumors with both hepatocyte and cholangiocyte differentiation
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• majority of large nodules are hepatocellular dysplasia, a precursor lesion of hepatocellular carcinoma
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• some lesions are diagnosed as intrahepatic cholangiocarcinoma by the appearance of adenocarcinoma showing tubular and/or papillary structures with a fibrous stroma; these tumor cells show loss of Pten expression
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• median survival is 46 days
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• seen in 5 month old mice
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• all mice start to show abdominal distension at about 5 weeks of age, frequently accompanied by jaundice and weight loss
• distension is due to hepatic enlargement and/or hemorrhagic ascites
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• tumors primarily show glandular morphology that resembles well-differentiated human cholangiocarcinoma and marker analysis indicates that tumors are intrahepatic cholangiocarcinoma
• in some cases, regions of moderately differentiated tumor with a cribriform appearance are seen
• no metastasis or invasion to other organs is seen
• tumors are frequently surrounded by dense fibrous stroma, indicating accumulation of fibrillar collagens
• stellate cells are activated and acquire a myofibroblast-like phenotype
• tumor cells show mucin production, a characteristic of epithelial cells in the bile duct
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• multiple solid tumors with various sizes are seen throughout the liver
• invasive tumors are apparent after 7 weeks of age, with abundant desmoplastic stroma or desmoplasia
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• various degrees of hyperplasia are seen in the bile ducts, characterized by increase in number and size and change in morphology, at 4 weeks of age
• at 5 weeks, a part of the hyperplastic ductal lesions at the hilum become enlarged and show a pattern of papillary growth
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• tumors primarily show glandular morphology that resembles well-differentiated human cholangiocarcinoma and marker analysis indicates that tumors are intrahepatic cholangiocarcinoma
• in some cases, regions of moderately differentiated tumor with a cribriform appearance are seen
• no metastasis or invasion to other organs is seen
• tumors are frequently surrounded by dense fibrous stroma, indicating accumulation of fibrillar collagens
• stellate cells are activated and acquire a myofibroblast-like phenotype
• tumor cells show mucin production, a characteristic of epithelial cells in the bile duct
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• various degrees of hyperplasia are seen in the bile ducts, characterized by increase in number and size and change in morphology, at 4 weeks of age
• at 5 weeks, a part of the hyperplastic ductal lesions at the hilum become enlarged and show a pattern of papillary growth
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• tumors primarily show glandular morphology that resembles well-differentiated human cholangiocarcinoma and marker analysis indicates that tumors are intrahepatic cholangiocarcinoma
• in some cases, regions of moderately differentiated tumor with a cribriform appearance are seen
• no metastasis or invasion to other organs is seen
• tumors are frequently surrounded by dense fibrous stroma, indicating accumulation of fibrillar collagens
• stellate cells are activated and acquire a myofibroblast-like phenotype
• tumor cells show mucin production, a characteristic of epithelial cells in the bile duct
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• multiple solid tumors with various sizes are seen throughout the liver
• invasive tumors are apparent after 7 weeks of age, with abundant desmoplastic stroma or desmoplasia
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| intrahepatic cholangiocarcinoma | DOID:4928 | J:254370 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• some die of stomach carcinomas by 3 months of age
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• some die by 3 months of age due to stomach carcinomas
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• some die of stomach carcinomas by 3 months of age
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• tumor formation is accelerated in comparison to conditional keratinocyte targeted Smad4tm2.1Cxd or Ptentm2Mak mutant mice
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• develop visible squamous papillomas on their backs at 2 months of age
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• some die of stomach carcinomas by 3 months of age
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• tumor formation is accelerated in comparison to conditional keratinocyte targeted Smad4tm2.1Cxd or Ptentm2Mak mutant mice
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• exhibit persistently proliferating follicular keratinocytes
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• exhibit enlarged cysts surrounded by a multilayered epithelium filled with keratinized debris or pigments
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• exhibit obvious hair loss 2 months after birth, about 1 month earlier than conditional keratinocyte targeted Smad4tm2.1Cxd mutant mice
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• outer root sheath is thicker at P18
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• hair follicles fail to go into catagen stage, indicating blocked regression
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• hair follicles have significantly more proliferating cells at P18 than conditional keratinocyte targeted Ptentm2Mak mutant mice
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• thickened epidermis is observed at P18
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• tumor formation is accelerated in comparison to conditional keratinocyte targeted Smad4tm2.1Cxd or Ptentm2Mak mutant mice
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• develop visible squamous papillomas on their backs at 2 months of age
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|
• exhibit persistently proliferating follicular keratinocytes
|
|
• exhibit enlarged cysts surrounded by a multilayered epithelium filled with keratinized debris or pigments
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• carcinoma develops in the prostate at different rates depending on age of mouse when tamoxifen administration occurs
• when tamoxifen is given to mice at two weeks of age, overt neoplasia and microinvasive carcinoma are evident 10 to 12 weeks later in one-third of mice
• when tamoxifen is given to mice 6 weeks of age, a more gradual progression to carcinoma occurs with overtly malignant lesions not present until 1 year of age
|
|
|
• when tamoxifen is given to mice at 2 weeks of age, hyperplastic regions as well as low grade PIN lesions and an increased number of apoptotic cells are evident 4 to 6 weeks later
• by 10-12 weeks post injection, all mice display increased proliferation of the prostate epithelium and high grade PIN lesions with a third of the mice having microinvasive carcinomas
• when tamoxifen is given to mice at 6 weeks of age, early hyperplastic lesions and increased proliferation rates of the prostate epithelium are evident 4 weeks later
• about half the mice exhibit advanced PIN lesions at 16-20 weeks after tamoxifen administration at 6 weeks of age
|
|
|
• carcinoma develops in the prostate at different rates depending on age of mouse when tamoxifen administration occurs
• when tamoxifen is given to mice at two weeks of age, overt neoplasia and microinvasive carcinoma are evident 10 to 12 weeks later in one-third of mice
• when tamoxifen is given to mice 6 weeks of age, a more gradual progression to carcinoma occurs with overtly malignant lesions not present until 1 year of age
|
|
|
• when tamoxifen is given to mice at 2 weeks of age, hyperplastic regions as well as low grade PIN lesions and an increased number of apoptotic cells are evident 4 to 6 weeks later
• by 10-12 weeks post injection, all mice display increased proliferation of the prostate epithelium and high grade PIN lesions with a third of the mice having microinvasive carcinomas
• when tamoxifen is given to mice at 6 weeks of age, early hyperplastic lesions and increased proliferation rates of the prostate epithelium are evident 4 weeks later
• about half the mice exhibit advanced PIN lesions at 16-20 weeks after tamoxifen administration at 6 weeks of age
|
|
|
• carcinoma develops in the prostate at different rates depending on age of mouse when tamoxifen administration occurs
• when tamoxifen is given to mice at two weeks of age, overt neoplasia and microinvasive carcinoma are evident 10 to 12 weeks later in one-third of mice
• when tamoxifen is given to mice 6 weeks of age, a more gradual progression to carcinoma occurs with overtly malignant lesions not present until 1 year of age
|
|
|
• when tamoxifen is given to mice at 2 weeks of age, hyperplastic regions as well as low grade PIN lesions and an increased number of apoptotic cells are evident 4 to 6 weeks later
• by 10-12 weeks post injection, all mice display increased proliferation of the prostate epithelium and high grade PIN lesions with a third of the mice having microinvasive carcinomas
• when tamoxifen is given to mice at 6 weeks of age, early hyperplastic lesions and increased proliferation rates of the prostate epithelium are evident 4 weeks later
• about half the mice exhibit advanced PIN lesions at 16-20 weeks after tamoxifen administration at 6 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mean survival time is 90.5 weeks of age
|
|
|
• mice show early formation of prostate tumors before 20 weeks of age
• tumors in 20 week old mice show an initial response to androgen deprivation therapy (by surgical castration), however by 8 weeks post-castration, mice develop castration-resistant prostate cancer in which tumors are insensitive to everolimus, a PI3K/AKT targeted therapy
• castration-resistant prostate tumors however are sensitive to a combination therapy of everolimus and U0126, a MEK1/2 inhibitor, showing increased apoptosis following treatment
|
|
|
• from 20 weeks, all mice develop adenocarcinomas in the lateral, dorsal, and ventral prostate lobes, however tumors in the anterior prostate are rare
|
|
|
• mice gradually develop prostatic intraepithelial neoplasia as early as 8 weeks in the dorsolateral lobes that progress to well-differentiated tumors by 15 weeks
|
|
|
• at 50-60 weeks of age, 10% of mice develop distant spread of tumor metastases primarily in the loco-regional lymph nodes and occasionally in lung and liver
• by 75-90 weeks of age, about 60% of mice show distant spread of tumor metastases
|
|
|
• mice show early formation of prostate tumors before 20 weeks of age
• tumors in 20 week old mice show an initial response to androgen deprivation therapy (by surgical castration), however by 8 weeks post-castration, mice develop castration-resistant prostate cancer in which tumors are insensitive to everolimus, a PI3K/AKT targeted therapy
• castration-resistant prostate tumors however are sensitive to a combination therapy of everolimus and U0126, a MEK1/2 inhibitor, showing increased apoptosis following treatment
|
|
|
• from 20 weeks, all mice develop adenocarcinomas in the lateral, dorsal, and ventral prostate lobes, however tumors in the anterior prostate are rare
|
|
|
• mice gradually develop prostatic intraepithelial neoplasia as early as 8 weeks in the dorsolateral lobes that progress to well-differentiated tumors by 15 weeks
|
|
|
• mice show early formation of prostate tumors before 20 weeks of age
• tumors in 20 week old mice show an initial response to androgen deprivation therapy (by surgical castration), however by 8 weeks post-castration, mice develop castration-resistant prostate cancer in which tumors are insensitive to everolimus, a PI3K/AKT targeted therapy
• castration-resistant prostate tumors however are sensitive to a combination therapy of everolimus and U0126, a MEK1/2 inhibitor, showing increased apoptosis following treatment
|
|
|
• from 20 weeks, all mice develop adenocarcinomas in the lateral, dorsal, and ventral prostate lobes, however tumors in the anterior prostate are rare
|
|
|
• mice gradually develop prostatic intraepithelial neoplasia as early as 8 weeks in the dorsolateral lobes that progress to well-differentiated tumors by 15 weeks
|
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:214242 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Urothelial hyperplasia and increased apoptosis in bladder epithelium of Ptentm2Mak/Ptentm2Mak Stk11tm1Keis/Stk11tm1Keis Tg(Cyp1a1-cre/ERT)1Dwi/0 mice
|
• mice injected with beta-napthoflavone and tamoxifen exhibit decreased survival after day 100 of induction, mostly due to bladder blockage
|
|
• mice injected with beta-napthoflavone and tamoxifen develop large papillary bladder tumors by day 125 of induction
• tumor tissue shows signs of spindle-shaped cells, squamous metaplasia, focal microvesicular change, and increase in nuclear-cytoplasmic ratio
|
|
• treatment with rapamycin reduces bladder size
• mice injected with beta-napthoflavone and tamoxifen exhibit enlarged bladders by 125 days of induction
|
|
• mice injected with beta-napthoflavone and tamoxifen develop large papillary bladder tumors by day 125 of induction
• tumor tissue shows signs of spindle-shaped cells, squamous metaplasia, focal microvesicular change, and increase in nuclear-cytoplasmic ratio
|
|
• by day 100 of induction with beta-napthoflavone and tamoxifen, mucosa of bladders is thickened
|
|
• mice injected with beta-napthoflavone and tamoxifen exhibit urothelial hyperplasia by day 50 and 100 of induction
• bladder epithelium of beta-napthoflavone and tamoxifen treated mice shows presence of apoptosis and vacuoles at day 50 of induction
• elevation in proliferation in the urothelium of mice injected with beta-napthoflavone and tamoxifen
• marker analysis indicates that bladder urothelial cells of beta-napthoflavone and tamoxifen injected mice exhibit characteristics of epithelial-mesenchymal transition, with loss of epithelial markers and increases in mesenchymal markers
• treatment with rapamycin reduces urothelial epithelium thickness and suppresses the epithelial-to-mesenchymal transition
|
|
• mice injected with beta-napthoflavone and tamoxifen show bladder obstruction due to tumors
|
|
• mice injected with beta-napthoflavone and tamoxifen exhibit enlarged bladders by 125 days of induction
• treatment with rapamycin reduces bladder size
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| urinary bladder cancer | DOID:11054 |
OMIM:109800 |
J:169565 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice injected with beta-napthoflavone and tamoxifen do not show any abnormal bladder morphology and do not develop bladder tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• liver is larger in 10 week old mice and further enlarged at 40 weeks
|
|
• liver weight per body weight ratio is increased 2-fold at 10 weeks and 3-fold at 40 weeks
|
|
• mild sinusoidal fibrogenic changes and accumulations of lobular inflammatory cells are seen by 40 weeks of age
|
|
• increase in hepatocyte proliferation at 10 weeks of age
• however, no differences in hepatocyte apoptosis are seen at 10 or 40 weeks of age
|
|
• liver is larger in 10 week old mice and further enlarged at 40 weeks
|
|
• liver weight per body weight ratio is increased 2-fold at 10 weeks and 3-fold at 40 weeks
|
|
• triglyceride levels are increased in the liver at 10 weeks of age and are highly elevated at 40 weeks of age
• however, no differences in liver levels of free fatty acids, free cholesterol, or phospholipids are seen
|
|
• hepatocytes acquire expression of an adipocyte-specific marker
|
|
• Mallory bodies are frequently seen in hepatocytes by 40 weeks of age
|
|
• absolute numbers of total liver cells are almost normal at 10 weeks of age but increased by 1.5-fold at 40 weeks
|
|
• cytoplasm of liver cells is weakly eosinophilic and contains numerous microvesicular vacuoles containing lipids at 10 weeks of age; vacuolar changes are seen mainly around the central vein
• steatotic changes are more prominent in male than female mice
• by 40 weeks of age, livers show fatty changes of increased severity throughout the hepatic lobule such that aged liver resembles adipocytes in fat tissues
• however, no fibrotic changes are seen in the liver
|
|
• hepatocellular carcinomas are seen in 5 of 6 males and 3 of 6 females; the hepatocellular carcinomas develop within liver adenomas and contain many fewer cytoplasmic lipid droplets than the adenomas
|
|
• macroscopic hepatic tumors are present in 66% of male and 30% of female mice at 40-44 weeks of age; nodular lesions resemble liver adenomas and cells with large droplets in the cytoplasm are prominent in most adenomas
|
|
• livers are light-colored at 10 weeks of age and homogenously white in color at 40 weeks
|
|
• cholesterol ester levels are increased in the liver at 10 weeks of age and are highly elevated at 40 weeks of age
|
|
• glucose levels are lower in fasted mutants both before and after oral glucose administration
|
|
• serum insulin levels are reduced at 12 weeks of age
|
|
• serum levels are elevated at 40 weeks of age but not at 10 weeks of age
|
|
• serum levels are elevated at 40 weeks of age but not at 10 weeks of age
|
|
• serum levels are elevated at 40 weeks of age but not at 10 weeks of age
|
|
• intraperitoneal insulin injection reduces glucose levels by a greater amount than in wild-type mice indicating insulin hypersensitivity
|
|
• 16-carbon monosaturated fatty acids (C16:1) and C18:1 fatty acids are increased in livers of 10 week old mice and C16:0, C16:1, C18:0, C18:1, and C18:2 fatty acids are increased in livers of 40 week old mice
|
|
• triglyceride levels are increased in the liver at 10 weeks of age and are highly elevated at 40 weeks of age
• however, no differences in liver levels of free fatty acids, free cholesterol, or phospholipids are seen
|
|
• hepatocellular carcinomas are seen in 5 of 6 males and 3 of 6 females; the hepatocellular carcinomas develop within liver adenomas and contain many fewer cytoplasmic lipid droplets than the adenomas
|
|
• macroscopic hepatic tumors are present in 66% of male and 30% of female mice at 40-44 weeks of age; nodular lesions resemble liver adenomas and cells with large droplets in the cytoplasm are prominent in most adenomas
|
|
• 2 mutants with hepatocellular carcinoma show lung metastasis
|
|
• mild sinusoidal fibrogenic changes and accumulations of lobular inflammatory cells are seen by 40 weeks of age
|
|
• increase in hepatocyte proliferation at 10 weeks of age
• however, no differences in hepatocyte apoptosis are seen at 10 or 40 weeks of age
|
|
• cholesterol ester levels are increased in the liver at 10 weeks of age and are highly elevated at 40 weeks of age
|
|
• hepatic hydrogen peroxide levels in the liver are increased 7-fold, indicating increased production of reactive oxygen species
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hepatocellular carcinoma | DOID:684 |
OMIM:114550 |
J:90905 | |
| steatotic liver disease | DOID:9452 |
OMIM:228100 |
J:90905 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in mice induced with beta-naphthoflavonein mice induced with beta-naphthoflavonein mice induced with beta-naphthoflavone
|
|
• in mice induced with beta-naphthoflavone
|
|
• in one mouse induced with beta-naphthoflavone
|
|
• in one mouse induced with beta-naphthoflavone
|
|
• in mice induced with beta-naphthoflavone
|
 |
• mice induced with beta-naphthoflavone exhibit atypical endometrial hyperplasia
|
|
• in mice induced with beta-naphthoflavone leading to euthanasia
|
| N |
• mice induced with beta-naphthoflavone exhibit normal crypt-villus architecture and physiology
|
|
• in mice induced with beta-naphthoflavonein mice induced with beta-naphthoflavonein mice induced with beta-naphthoflavone
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• thymic lymphomas develop with a mean age of onset of 60 days, similar to that seen in T cell-specific Pten homozygotes
|
|
• thymic lymphomas develop with a mean age of onset of 60 days, similar to that seen in T cell-specific Pten homozygotes
|
|
• thymic lymphomas develop with a mean age of onset of 60 days, similar to that seen in T cell-specific Pten homozygotes
|
|
• thymic lymphomas develop with a mean age of onset of 60 days, similar to that seen in T cell-specific Pten homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• following induction with tamoxifen in utero or in adult mice, crypt-villi architecture and physiology are normal
|
|
• when induced with tamoxifen in utero, mice develop a shaggy or ruffled coat
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 10 weeks of age
|
|
• by 40 weeks of age, livers contain Mallory bodies, ballooning hepatocytes and accumulation of lobular inflammatory cells
|
|
• beginning at 10 weeks of age, mice exhibit enlargement of the liver that progressed further by 40 weeks of age
|
|
• at 10 and 40 weeks of age
|
|
• at 10 and 40 weeks of age
|
|
• at 10 weeks of age, the cytoplasm of hepatocytes contain lipid-filled micro- and macro-vesicular vacuoles unlike in wild-type mice
• at 40 weeks of age, micro- and macro-vesicular vacuoles coalesce to and displace the nucleus
|
|
• by 40 weeks of age, livers contain Mallory bodies
|
|
• at 10 weeks of age
|
|
• at 74 to 78 weeks of age, 83% of males and 50% of females exhibit hepatocellular carcinomas that develop within liver adenomas and contain fewer lipid droplets than the adenomas
• 2 of 6 mice exhibit metastasis of hepatocellular carcinomas to the lungs
|
|
• at 40 weeks of age, 66% of males and 30% of females exhibit liver adenomas that contain large lipid droplets
|
|
• at 40 weeks of age
|
|
• beginning at 10 weeks of age, mice exhibit a pale liver that is white by 40 weeks of age
|
|
• the polyploid mononuclear hepatocyte population is enriched in the liver of 3 and 10 month old mutants
• highly polyploid hepatocytes are also present in hepatocellular tumors in the livers
|
|
• at 10 weeks of age, hepatocyte proliferation is increased while apoptosis rates are normal
|
|
• at 74 to 78 weeks of age, 83% of males and 50% of females exhibit hepatocellular carcinomas that develop within liver adenomas and contain fewer lipid droplets than the adenomas
• 2 of 6 mice exhibit metastasis of hepatocellular carcinomas to the lungs
|
|
• at 40 weeks of age, 66% of males and 30% of females exhibit liver adenomas that contain large lipid droplets
|
|
• at 40 weeks of age
|
|
• at 40 weeks of age
|
|
• at 10 and 40 weeks of age
|
|
• at 10 and 40 weeks of age
|
|
• at 10 weeks of age
|
|
• at 10 weeks of age, hepatocyte proliferation is increased while apoptosis rates are normal
|
|
• beginning at 10 weeks of age, mice exhibit enlargement of the liver that progressed further by 40 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hepatocellular carcinoma | DOID:684 |
OMIM:114550 |
J:138099 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen treated mice exhibit shortened lifespan
|
|
• tamoxifen treated mice exhibit accelerated formation of lung and pancreatic tumors compared to single Tg(RasE)290Biat transgenics
|
|
• tamoxifen treated mice exhibit accelerated formation of lung and pancreatic tumors compared to single Tg(RasE)290Biat transgenics
|
|
• tamoxifen treated mice exhibit accelerated formation of lung and pancreatic tumors compared to single Tg(RasE)290Biat transgenics
|
|
• tamoxifen treated mice exhibit accelerated formation of lung and pancreatic tumors compared to single Tg(RasE)290Biat transgenics
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants exhibit increased susceptibility to N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder cancer, with 50% developing transitional cell carcinomas (TCC) and 25% developing carcinoma in situ (CIS) and dysplasia compared to 8% of wild-type mice developing TCC and 8% developing CIS and dysplasia at 16 weeks after BBN administration
|
|
• mutants develop spontaneous superficial papillary transitional cell carcinomas, with an incidence of 10% in 40-80 week old mutants
|
|
• mutants develop spontaneous superficial papillary transitional cell carcinomas, with an incidence of 10% in 40-80 week old mutants
|
|
• two mutants exhibit hydronephrosis due to presence of large cancers in the bladder or renal pelvis
|
|
• thickening of the urothelial layer by 8 weeks of age due to increases in cell number and cell size
• urothelial hyperplasia is due to increased proliferation of bladder epithelial cells
|
|
• absolute numbers of bladder epithelial cells are increased 1.6-fold over wild-type levels at 8 weeks of age and 2.6-fold at 48 weeks of age
• size of individual bladder epithelial cells is greater than control cells; increase in size is not due to polyploidy as both diploid and tetraploid cell fractions are increased
|
|
• mutants exhibit increased susceptibility to N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder cancer, with 50% developing transitional cell carcinomas (TCC) and 25% developing carcinoma in situ (CIS) and dysplasia compared to 8% of wild-type mice developing TCC and 8% developing CIS and dysplasia at 16 weeks after BBN administration
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| urinary bladder cancer | DOID:11054 |
OMIM:109800 |
J:113388 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• females develop mammary tumors with a latency of 11.3 months
• expression analysis indicates that mammary tumors resemble human claudin-low triple-negative-like breast cancer and show more mesenchymal features
|
|
|
• about 72% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer, with the rest showing mixed mesenchymal plus adenocarcinomas or differentiated adenocarcinomas
|
|
|
• about 72% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer
|
|
|
• 17% of mammary tumors are adenomyoepithelioma
|
|
|
• females develop mammary tumors with a latency of 11.3 months
• expression analysis indicates that mammary tumors resemble human claudin-low triple-negative-like breast cancer and show more mesenchymal features
|
|
|
• about 72% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer, with the rest showing mixed mesenchymal plus adenocarcinomas or differentiated adenocarcinomas
|
|
|
• females develop mammary tumors with a latency of 11.3 months
• expression analysis indicates that mammary tumors resemble human claudin-low triple-negative-like breast cancer and show more mesenchymal features
|
|
|
• about 72% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer, with the rest showing mixed mesenchymal plus adenocarcinomas or differentiated adenocarcinomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:224955 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice develop mammary tumors after a latency of 26.4 months with 70% penetrance
|
|
|
• 25% of mammary tumors are adenosquamous carcinoma and 4% are acinar or poorly differentiated adenocarcinoma
|
|
|
• pregnancy accelerates tumor formation
|
|
|
• 4% of mammary tumors are spindle-cell/adenosarcoma
|
|
|
• 67% of mammary tumors are adenomyoepithelioma
|
|
|
• mice develop mammary tumors after a latency of 26.4 months with 70% penetrance
|
|
|
• 25% of mammary tumors are adenosquamous carcinoma and 4% are acinar or poorly differentiated adenocarcinoma
|
|
|
• pregnancy accelerates tumor formation
|
|
|
• mice develop mammary tumors after a latency of 26.4 months with 70% penetrance
|
|
|
• 25% of mammary tumors are adenosquamous carcinoma and 4% are acinar or poorly differentiated adenocarcinoma
|
|
|
• pregnancy accelerates tumor formation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• females develop mammary tumors with a latency of 9.8 months
• expression analysis indicates that mammary tumors resemble human claudin-low triple-negative-like breast cancer and show more mesenchymal features
|
|
|
• about 67% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer, with the rest showing mixed mesenchymal plus adenocarcinomas or differentiated adenocarcinomas
|
|
|
• about 67% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer
|
|
|
• 11% of mammary tumors are adenomyoepithelioma
|
|
|
• females develop mammary tumors with a latency of 9.8 months
• expression analysis indicates that mammary tumors resemble human claudin-low triple-negative-like breast cancer and show more mesenchymal features
|
|
|
• about 67% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer, with the rest showing mixed mesenchymal plus adenocarcinomas or differentiated adenocarcinomas
|
|
|
• females develop mammary tumors with a latency of 9.8 months
• expression analysis indicates that mammary tumors resemble human claudin-low triple-negative-like breast cancer and show more mesenchymal features
|
|
|
• about 67% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer, with the rest showing mixed mesenchymal plus adenocarcinomas or differentiated adenocarcinomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:224955 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• females develop mammary tumors after a latency of 15.2 months with almost complete penetrance
• nearly all mice succumb to cancer by 18 months of age
|
|
|
• 20% of mammary tumors are adenosquamous carcinoma and 7% are acinar or poorly differentiated adenocarcinoma
|
|
|
• pregnancy accelerates tumor formation
|
|
|
• 3% of mammary tumors are spindle-cell/adenosarcoma
|
|
|
• 70% of mammary tumors are adenomyoepithelioma
|
|
|
• females develop mammary tumors after a latency of 15.2 months with almost complete penetrance
• nearly all mice succumb to cancer by 18 months of age
|
|
|
• 20% of mammary tumors are adenosquamous carcinoma and 7% are acinar or poorly differentiated adenocarcinoma
|
|
|
• pregnancy accelerates tumor formation
|
|
|
• females develop mammary tumors after a latency of 15.2 months with almost complete penetrance
• nearly all mice succumb to cancer by 18 months of age
|
|
|
• 20% of mammary tumors are adenosquamous carcinoma and 7% are acinar or poorly differentiated adenocarcinoma
|
|
|
• pregnancy accelerates tumor formation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as in mice with wild-type Coro1c in tamoxifen-treated mice
|
|
• as in mice with wild-type Coro1c in tamoxifen-treated mice
|
|
• as in mice with wild-type Coro1c in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants are unusually resistant to handling by 6 weeks of age
|
|
• in the Morris water maze, mutants learn the visible platform task as well as controls but show a trend toward slower acquisition
• in the submerged platform Morris water maze, mutants do not learn as quickly as controls, showing increased latency and longer distance traveled to reach the platform
• in the probe trial, mutants show no preference for time spent in each quadrant unlike controls which spend more time in the target quadrant
|
|
• mice show increased anxiety-like behavior in the open field where they spend less time in the center zone and show a lower ratio of center versus periphery time
• in the dark/light apparatus, mutants show longer latencies to enter the light side, spending most of their time on the dark side
• however, in the elevated plus maze, mutants do not show anxiety-like behavior
|
|
• mice exhibit a greater tendency to swim along the edge of the Morris water maze
|
|
• mutants exhibit increased initial startle responses to a 120 dB white noise stimulation
• however, mice show similar startle responses as controls upon repeated startle stimulation indicating normal habituation
|
|
• mutants exhibit normal locomotor activity in less stressful environments but hyperactivity under more stressful conditions
• mice are hyperactive in the bright environment of the open field, traveling further at an increased average speed
• however, in the dark/light boxes and in the enclosed, darker environments of the locomotor apparatus, locomotor activity is normal
|
|
• mice exhibit normal coordination on the accelerating rotarod test during initial trials, however they perform better during subsequent trials indicating better performance in a repetitive behavior
|
|
• mortality of pups by P5 from mutant females fertilized by wild-type males is increased, indicating defects in maternal care
|
|
• mutants show little nest forming activity
|
|
• no naive mutant males make female mice pregnant and active sexual behavior is not seen by males, however fertility of males is not analyzed
|
|
• mice show decreased social interaction and abnormal social learing in several tests without change in novel object exploration, preference for social novelty, or olfaction
|
|
• 6 of 52 mutants exhibited sporadic seizures during testing
• EEG/EMG recordings show that all mice develop spontaneous seizures during the light phase; repetitive spike-wave patterns, sometimes accompanied by rhythmic slow activity, and continuous spike-wave bursting are noted
• incidence of seizures is 0.67 per mouse per day, and the mean duration is 10 minutes 50 seconds
• sound and tactile stimuli do not induce seizures
|
|
• mice show progressive macrocephaly, confined to the forebrain (cortex and hippocampus)
|
|
• 6 of 52 mutants exhibited sporadic seizures during testing
• EEG/EMG recordings show that all mice develop spontaneous seizures during the light phase; repetitive spike-wave patterns, sometimes accompanied by rhythmic slow activity, and continuous spike-wave bursting are noted
• incidence of seizures is 0.67 per mouse per day, and the mean duration is 10 minutes 50 seconds
• sound and tactile stimuli do not induce seizures
|
|
• progressive increase in brain weight after 2 months of age
|
|
• aging mice show compression or absence of the CA1 region
|
|
• aging mice show foliation of the dentate gyrus
• disorganized dentate gyrus granular layer
• progressive increase in the thickness of MAP2+ dentate molecular layer
|
|
• progressive enlargement with age
|
|
• dentate gyrus shows progressive enlargement of the mossy fiber tract
• mice show elongated and dispersed mossy fiber tract from the granular layer of the dentate gyrus
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• ectopic neuronal processes extending from the cell bodies into the dentate gyrus polymorphic layer are seen in the dentate gyrus at 3 months of age
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• dendritic hypertrophy and ectopy in adult dentate gyrus
• at 8 months of age, dendrites of ectopic neurons extending into the dentate gyrus polymorphic layer are longer and thicker and dendrites extending into the molecular layer are thicker
• at 8 months, dendritic arbors in the molecular layer of the dentate gyrus are increased in length
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• 24.9% increase in dendritic spine density within the molecular layer of the dentate gyrus
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• synapses of the dentate gyrus are abnormal
• mossy fiber synapses span a larger area
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• the dentate gyrus inner molecular layer shows an increase in presynaptic vesicle number
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• at 8 months of age, ectopic neuronal processes extend into the polymorphic and molecular layers of the dentate gyrus
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• Pten-negative neurons are larger than Pten-positive neurons at 4 weeks of age
• progressive increase in neuronal soma diameter indicating soma hypertrophy
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• sensorimotor gating is impaired
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| macrocephaly-autism syndrome | DOID:0060867 |
OMIM:605309 |
J:109635 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• exhibit an increase in the anterior wall thickness, however see no evidence of wall thinning or tissue fibrosis and heart rate is normal
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• increase in both the length and width of cardiomyocytes
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• increased in heart size is detectable in newborns
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• seen at 10 weeks and 12 months of age, however do not observe cardiac decompensation or dilated cardiomyopathy
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• exhibit an increase in the left ventricle mass
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• decrease in fractional shortening, velocity of circumferential fiber shortening, peak aortic outflow velocity, dP/dT-max and dP/dT-min, indicating impaired contractile heart function
• individual cardiomyocytes display a reduction in contractility as shown by a reduction in percent cell shortening and positive and negative dL/dTs
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• increase in both the length and width of cardiomyocytes
|
|
• decrease in fractional shortening, velocity of circumferential fiber shortening, peak aortic outflow velocity, dP/dT-max and dP/dT-min, indicating impaired contractile heart function
• individual cardiomyocytes display a reduction in contractility as shown by a reduction in percent cell shortening and positive and negative dL/dTs
|
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• increased in heart size is detectable in newborns
|
|
• seen at 10 weeks and 12 months of age, however do not observe cardiac decompensation or dilated cardiomyopathy
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• display a reduction in heart size similar to that seen in single Tg(Myh6-Pik3ca)1Siz mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• significantly enlarged compared to wild-type and single homozygous Pik3cgtm1Pngr mice
|
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• extent of cardiac hypertrophy is similar to that seen in mice with cardiomyocyte-specific inactivation of Pten
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• hearts are hypercontractile as assessed by increased fractional shortening, velocity or circumferential fiber shortening, and peak aortic outflow velocity
• individual cardiomyocytes display increased contractility despite the hypertrophy
|
|
• hearts are hypercontractile as assessed by increased fractional shortening, velocity or circumferential fiber shortening, and peak aortic outflow velocity
• individual cardiomyocytes display increased contractility despite the hypertrophy
|
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• significantly enlarged compared to wild-type and single homozygous Pik3cgtm1Pngr mice
|
|
• extent of cardiac hypertrophy is similar to that seen in mice with cardiomyocyte-specific inactivation of Pten
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in tamoxifen-treated mice
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• in tamoxifen-treated mice
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• in tamoxifen-treated mice
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die within 19 weeks (range 7-19 weeks, average 11.5 weeks) after AdCre injection into the ovarian bursa and development of ovarian tumors
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• 8-10 week old mice injected with an adenovirus expressing cre recombinase (AdCre) into the right ovarian bursa develop ovarian carcinoma with 100% penetrance within 6 weeks of AdCre injection
• tumors show similarity to human ovarian endometrioid adenocarcinoma, with formation of distinct glands and occasional foci of squamous differentiation
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• 8-10 week old mice injected with an adenovirus expressing cre recombinase (AdCre) into the right ovarian bursa develop ovarian carcinoma with 100% penetrance within 6 weeks of AdCre injection
• tumors show similarity to human ovarian endometrioid adenocarcinoma, with formation of distinct glands and occasional foci of squamous differentiation
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• 76% of ovarian bursa AdCre injected mice develop hemorrhagic ascites and 21% develop overt peritoneal dissemination of tumors
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• 8-10 week old mice injected with an adenovirus expressing cre recombinase (AdCre) into the right ovarian bursa develop ovarian carcinoma with 100% penetrance within 6 weeks of AdCre injection
• tumors show similarity to human ovarian endometrioid adenocarcinoma, with formation of distinct glands and occasional foci of squamous differentiation
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:120955 | |
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 11/19/2024 MGI 6.24 |
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