Analysis Tools|
Allele Symbol Allele Name Allele ID |
Ctnnb1tm1Mmt targeted mutation 1, Makoto M Taketo MGI:1858008 |
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| Summary |
66 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• adults receiving a single tamoxifen dose at P60 demonstrated numerous microadenomas in the small intestines when analyzed at P105
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• adults receiving a single tamoxifen dose at P60 and analyzed at P105 show an expansion of the proliferative compartment from crypts to more distal epithelium
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• adults receiving a single tamoxifen dose at P60 and analyzed at P105 show a general tissue disorganization of the small intestine
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• adults receiving a single tamoxifen dose at P60 demonstrated numerous microadenomas in the small intestines when analyzed at P105
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• adults receiving a single tamoxifen dose at P60 and analyzed at P105 show an expansion of the proliferative compartment from crypts to more distal epithelium
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• the majority of females develop mammary gland tumors between 25 and 40 weeks postpartum
• tumors are squamous metaplasia
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• the majority of females develop mammary gland tumors between 25 and 40 weeks postpartum
• tumors are squamous metaplasia
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• the majority of females develop mammary gland tumors between 25 and 40 weeks postpartum
• tumors are squamous metaplasia
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tumor onset is more rapid than in either single mutant, with almost all females showing mammary gland tumors by 2 weeks postpartum
• tumors exhibit a mixed phenotype, with areas resembling basaloid hyperplasia and squamous metaplasia
• tumors exhibit morphological, gene and protein expression profile characteristics of basal breast cancers; they are HER2/ErbB2, ER, and PR negative, and express metastasis-associated genes
• treatment with the Wnt and Met inhibitors ICG-001 or PHA 665752 results in a moderate decrease in mammary gland tumor volume, treatment with a combination of these or with a small molecule inhibitor AMD3100, an agonist of CXCR4 receptor, strongly suppresses tumor onset up to 16 days, and treatment with all three shows the strongest inhibition in tumor size
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• in a few cases, virgin females develop small tumors
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• mammary gland tissues of breeding females show an expansion of CD24+/CD29(medium) and CD24+/CD49(hi) cells and depletion of CD24(low)/CD29+ cells, indicating expansion of a population of cells with progenitor and stem cell characteristics
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• production of milk protein beta-casein after pregnancy is not detected indicating a block in normal mammary gland differentiation
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• lobuloalveolar hyperplasia
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• tumor onset is more rapid than in either single mutant, with almost all females showing mammary gland tumors by 2 weeks postpartum
• tumors exhibit a mixed phenotype, with areas resembling basaloid hyperplasia and squamous metaplasia
• tumors exhibit morphological, gene and protein expression profile characteristics of basal breast cancers; they are HER2/ErbB2, ER, and PR negative, and express metastasis-associated genes
• treatment with the Wnt and Met inhibitors ICG-001 or PHA 665752 results in a moderate decrease in mammary gland tumor volume, treatment with a combination of these or with a small molecule inhibitor AMD3100, an agonist of CXCR4 receptor, strongly suppresses tumor onset up to 16 days, and treatment with all three shows the strongest inhibition in tumor size
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• in a few cases, virgin females develop small tumors
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• mammary gland tissues of breeding females show an expansion of CD24+/CD29(medium) and CD24+/CD49(hi) cells and depletion of CD24(low)/CD29+ cells, indicating expansion of a population of cells with progenitor and stem cell characteristics
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• production of milk protein beta-casein after pregnancy is not detected indicating a block in normal mammary gland differentiation
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• lobuloalveolar hyperplasia
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• tumor onset is more rapid than in either single mutant, with almost all females showing mammary gland tumors by 2 weeks postpartum
• tumors exhibit a mixed phenotype, with areas resembling basaloid hyperplasia and squamous metaplasia
• tumors exhibit morphological, gene and protein expression profile characteristics of basal breast cancers; they are HER2/ErbB2, ER, and PR negative, and express metastasis-associated genes
• treatment with the Wnt and Met inhibitors ICG-001 or PHA 665752 results in a moderate decrease in mammary gland tumor volume, treatment with a combination of these or with a small molecule inhibitor AMD3100, an agonist of CXCR4 receptor, strongly suppresses tumor onset up to 16 days, and treatment with all three shows the strongest inhibition in tumor size
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• in a few cases, virgin females develop small tumors
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:206839 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• appearance of mammary tumors in postpartum females is delayed compared to triple Ctnnb1tm1Mmt Tg(Wap-cre)11738Mam Tg(Wap-Hgf)402Mig mutants, with tumors developing at 7 weeks postpartum rather than 2 weeks
• tumors are smaller in females 2 weeks postpartum than in triple mutants
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• appearance of mammary tumors in postpartum females is delayed compared to triple Ctnnb1tm1Mmt Tg(Wap-cre)11738Mam Tg(Wap-Hgf)402Mig mutants, with tumors developing at 7 weeks postpartum rather than 2 weeks
• tumors are smaller in females 2 weeks postpartum than in triple mutants
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• appearance of mammary tumors in postpartum females is delayed compared to triple Ctnnb1tm1Mmt Tg(Wap-cre)11738Mam Tg(Wap-Hgf)402Mig mutants, with tumors developing at 7 weeks postpartum rather than 2 weeks
• tumors are smaller in females 2 weeks postpartum than in triple mutants
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants on a doxycycline diet exhibit craniofacial malformations
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• 35% of mutants on a doxycycline diet for at least 3 weeks starting at P25 die during the 12 weeks following doxycycline administration; males and females die at similar rates
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• urothelia of males on the doxycycline diet is more severely affected than in females
• increase in urothelial basal cell proliferation is seen in mutants fed doxycycline
• bladders of males 5 weeks after doxycline treatment show a higher proliferation index than females at the same stage
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• 24% of the remaining surviving mutants on a doxycycline diet for at least 3 weeks starting at P25 exhibit tumors within the bladder lumen; 11 mutants have single tumor and 18 have multifoci tumors
• tumors in doxycline fed mutants resemble low-grade papillary urothelial carcinoma, exhibit polypoid structure, and the urothelium has lost its typical polarity and shows nuclear atypia, high mitogenic activity, and vascular infiltration
• however, no nuclear pleomorphism or muscle invasion is seen
• 45% of males on the doxycycline diet develop bladder tumors compared to 3% of females on the diet
• only 12.5% of castrated males after 3 months of doxycycline treatment develop luminal tumors and cell proliferation is 20% less than in noncastrated males
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• 24% of the remaining surviving mutants on a doxycycline diet for at least 3 weeks starting at P25 exhibit tumors within the bladder lumen; 11 mutants have single tumor and 18 have multifoci tumors
• tumors in doxycline fed mutants resemble low-grade papillary urothelial carcinoma, exhibit polypoid structure, and the urothelium has lost its typical polarity and shows nuclear atypia, high mitogenic activity, and vascular infiltration
• however, no nuclear pleomorphism or muscle invasion is seen
• 45% of males on the doxycycline diet develop bladder tumors compared to 3% of females on the diet
• only 12.5% of castrated males after 3 months of doxycycline treatment develop luminal tumors and cell proliferation is 20% less than in noncastrated males
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| urinary bladder cancer | DOID:11054 |
OMIM:109800 |
J:202618 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants succumb to tumors rapidly, dying between P75 and P90
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• rapidly develop aggressive tumors in the salivary glands
• tumors contain transplantable and hyperproliferative tumor propagating cells (CD24+CD29+)
• treatment of cultured CD24+CD29+ tumor cells with the canonical Wnt inhibitor ICG-001 blocks proliferation of these cells
• CD24+CD29+ tumor propagating cells from salivary gland tumors exhibit unrestricted self-renewal in salisphere culture
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• tumors arise from the submandibular salivary glands and are classified as salivary gland squamous cell carcinoma
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• rapidly develop aggressive tumors in the salivary glands
• tumors contain transplantable and hyperproliferative tumor propagating cells (CD24+CD29+)
• treatment of cultured CD24+CD29+ tumor cells with the canonical Wnt inhibitor ICG-001 blocks proliferation of these cells
• CD24+CD29+ tumor propagating cells from salivary gland tumors exhibit unrestricted self-renewal in salisphere culture
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• rapidly develop aggressive tumors in the salivary glands
• tumors contain transplantable and hyperproliferative tumor propagating cells (CD24+CD29+)
• treatment of cultured CD24+CD29+ tumor cells with the canonical Wnt inhibitor ICG-001 blocks proliferation of these cells
• CD24+CD29+ tumor propagating cells from salivary gland tumors exhibit unrestricted self-renewal in salisphere culture
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• excessive supernumerary hair follicles in the skin
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• rapidly develop aggressive tumors in the salivary glands
• tumors contain transplantable and hyperproliferative tumor propagating cells (CD24+CD29+)
• treatment of cultured CD24+CD29+ tumor cells with the canonical Wnt inhibitor ICG-001 blocks proliferation of these cells
• CD24+CD29+ tumor propagating cells from salivary gland tumors exhibit unrestricted self-renewal in salisphere culture
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• rapidly develop aggressive tumors in the salivary glands
• tumors contain transplantable and hyperproliferative tumor propagating cells (CD24+CD29+)
• treatment of cultured CD24+CD29+ tumor cells with the canonical Wnt inhibitor ICG-001 blocks proliferation of these cells
• CD24+CD29+ tumor propagating cells from salivary gland tumors exhibit unrestricted self-renewal in salisphere culture
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| salivary gland carcinoma | DOID:0050904 | J:199091 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 40 days after tamoxifen treatment, mice have developed numerous polyps
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal bone formation
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• impaired
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• impaired
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• impaired
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• impaired
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• with 2 low doses of tamoxifen given at 6 weeks, most mice display obvious pituitary tumors between 3 and 5 months upon necropsy; pituitaries of remaining animals contained small tumors in the anterior lobe upon histological analysis
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• at E15.5, embryos show an enlarged anterior pituitary, with foci of accumulation of beta-catenin when tamoxifen induction is done at E10.5; clusters are observed to contain undifferentiated cells that do not express proliferation marker Ki67
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• with 2 low doses of tamoxifen given at 6 weeks, most mice display obvious pituitary tumors between 3 and 5 months upon necropsy; pituitaries of remaining animals contained small tumors in the anterior lobe upon histological analysis
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• at E15.5, embryos show an enlarged anterior pituitary, with foci of accumulation of beta-catenin when tamoxifen induction is done at E10.5; clusters are observed to contain undifferentiated cells that do not express proliferation marker Ki67
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• with 2 low doses of tamoxifen given at 6 weeks, most mice display obvious pituitary tumors between 3 and 5 months upon necropsy; pituitaries of remaining animals contained small tumors in the anterior lobe upon histological analysis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• doxycycline-treated mice exhibit normal bone formation and numbers of osteoblasts
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• impaired in doxycycline-treated mice
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• in doxycycline-treated mice
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• as early as P15 in doxycycline-treated mice
• 27-fold from 10 months of age in doxycycline-treated mice
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• in doxycycline-treated mice
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• 4.6-fold increase in trabecular bone surface and a smaller bone surface to bone volume in doxycycline-treated mice
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• trabecular, cortical and total volume as early as P15 in doxycycline-treated mice
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• 3.6-fold with reduced trabecular separation in doxycycline-treated mice
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• 8.5-fold in doxycycline-treated mice
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• severe in doxycycline-treated mice
• in mice following adult onset activation with doxycycline
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• in doxycycline-treated mice
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• impaired in doxycycline-treated mice
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• in doxycycline-treated mice
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• at 4 months in doxycycline-treated mice
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• at 10 months in doxycycline-treated mice
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• in doxycycline-treated mice
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• gradual in doxycycline-treated mice
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• impaired in doxycycline-treated mice
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• impaired in doxycycline-treated mice
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• in doxycycline-treated mice
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• gradual in doxycycline-treated mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• by 3 months of age, all mice develop WNT-subgroup medulloblastomas
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• by 3 months of age, all mice develop WNT-subgroup medulloblastomas
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• by 11 months, 4% of mice develop WNT-subgroup medulloblastomas
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• by 11 months, 4% of mice develop WNT-subgroup medulloblastomas
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants are born in expected numbers but die within hours of birth
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• rudimentary kidneys are cystic with only a only a few immature glomeruli and show random disorganized nephrogenic aggregates at periphery
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• about 20% of E18.5 embryos or neonatal pups exhibit hypoplastic rudimentary kidneys
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• most kidneys show some degree of hypoplasia
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• hydroureter with hypoplasia is observed at E18.5 and in PO pups with about 73.5% incidence; these kidneys also exhibit dilated tubules
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• rudimentary kidneys are cystic with only a only a few immature glomeruli and show random disorganized nephrogenic aggregates at periphery
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die 50 days following administration of tamoxifen
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• beginning 22 days following administration of tamoxifen
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• the number of proliferating cells within crypts is increased 15 days following administration of tamoxifen
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• beginning 22 days following administration of tamoxifen
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• the number of proliferating cells within crypts is increased 15 days following administration of tamoxifen
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• polysyndactyly and ectopic limb phenotypes are rescued
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• some mice exhibit ectopic limbs in the flank ectoderm and ventral ectoderm
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die prior to day 300
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• mice exhibit keratinized squamous metaplasia in the bulbourethral gland unlike wild-type mice
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• all mice develop diffuse, locally invasive carcinomas in the prostate that develop from solid or sheet-like proliferation with occasional rosette structures, nuclear atypia, apoptotic bodies, and mitosis unlike in wild-type mice
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• all mice develop diffuse, locally invasive carcinomas in the prostate that develop from solid or sheet-like proliferation with occasional rosette structures, nuclear atypia, apoptotic bodies, and mitosis unlike in wild-type mice
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• mice exhibit keratinized squamous metaplasia in the urethral gland unlike wild-type mice
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• mice exhibit keratinized squamous metaplasia in the bulbourethral gland unlike wild-type mice
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• all mice develop diffuse, locally invasive carcinomas in the prostate that develop from solid or sheet-like proliferation with occasional rosette structures, nuclear atypia, apoptotic bodies, and mitosis unlike in wild-type mice
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• mice exhibit keratinized squamous metaplasia in the urethral gland unlike wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop aggressive adenocarcinomas that occur with much higher frequency than in single Ctnnb1tm1Mmt conditional mutants, developing prostatic invasive adenocarcinomas as early as 7 months of age
• 4 of 4 mice show intracystic adenocarcinoma at 6-9 months of age, with 1 of 4 mice showing invasive adenocarcinoma
• 13 of 13 mice show intracystic adenocarcinoma at 9 months or older, with 5 of 13 showing invasive adenocarcinoma
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• mice develop PIN lesions starting at 4-6 weeks of age, with 5 of 5 mice showing high grade PIN before 6 months of age
• mice develop more severe PIN lesions and faster disease progression than single Ctnnb1tm1Mmt conditional mutants
• lesions in the anterior, dorsal, and lateral prostate lobes are more severe than in the ventral prostate
• typical cribriform and papilliferous structures completely fill the lumen of prostatic glands
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• mice develop aggressive adenocarcinomas that occur with much higher frequency than in single Ctnnb1tm1Mmt conditional mutants, developing prostatic invasive adenocarcinomas as early as 7 months of age
• 4 of 4 mice show intracystic adenocarcinoma at 6-9 months of age, with 1 of 4 mice showing invasive adenocarcinoma
• 13 of 13 mice show intracystic adenocarcinoma at 9 months or older, with 5 of 13 showing invasive adenocarcinoma
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• mice develop PIN lesions starting at 4-6 weeks of age, with 5 of 5 mice showing high grade PIN before 6 months of age
• mice develop more severe PIN lesions and faster disease progression than single Ctnnb1tm1Mmt conditional mutants
• lesions in the anterior, dorsal, and lateral prostate lobes are more severe than in the ventral prostate
• typical cribriform and papilliferous structures completely fill the lumen of prostatic glands
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• mice develop aggressive adenocarcinomas that occur with much higher frequency than in single Ctnnb1tm1Mmt conditional mutants, developing prostatic invasive adenocarcinomas as early as 7 months of age
• 4 of 4 mice show intracystic adenocarcinoma at 6-9 months of age, with 1 of 4 mice showing invasive adenocarcinoma
• 13 of 13 mice show intracystic adenocarcinoma at 9 months or older, with 5 of 13 showing invasive adenocarcinoma
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• mice develop PIN lesions starting at 4-6 weeks of age, with 5 of 5 mice showing high grade PIN before 6 months of age
• mice develop more severe PIN lesions and faster disease progression than single Ctnnb1tm1Mmt conditional mutants
• lesions in the anterior, dorsal, and lateral prostate lobes are more severe than in the ventral prostate
• typical cribriform and papilliferous structures completely fill the lumen of prostatic glands
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| prostate cancer | DOID:10283 |
OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959 |
J:284956 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die within 14-18 days of final injection of polyI:polyC used to induce transgene expression and subsequent Ctnnb1 deletion; no treated controls die
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• some induced mice show disrupted bone architecture with enhanced trabecular bone structures
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• some induced mutants display hepatoblastoma
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• some induced mice display skin fibrosis
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• some induced mutants display hepatoblastoma
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die within 14-18 days of final injection of polyI:polyC used to induce transgene expression and subsequent Ctnnb1 deletion; no treated controls die
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• some induced mice show disrupted bone architecture with enhanced trabecular bone structures
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• some induced mutants display hepatoblastoma
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• some induced mice display skin fibrosis
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• some induced mutants display hepatoblastoma
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• presence of nests of dysplastic cells are seen in the ovaries of newborn mice and E20.5, but not E18.5, indicating that tumor growth begins perinatally
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• females develop ovarian granulosa cell bilateral tumors with 100% penetrance from an early age
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• 100% penetrance of aggressive testicular cancer
• tumors are first observable at 5 weeks of age, and by 3 months of age, about 70% of mice have unilateral testicular tumors and 30% have bilateral tumors
• tumors exhibit characteristics of granulosa cell tumors of the testis and not Sertoli cell tumors
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• metastasis is not observed, but this might be that mice do not have sufficient time to develop metastasis due to early lethality, however, when granulosa cell tumors are removed at 6 weeks of age, mice show development of large lung metastases 6-16 weeks later, indicating that tumors indeed are metastatic
(J:142150)
• 44% of mice develop pulmonary metastases by 4 months
(J:149060)
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• presence of nests of dysplastic cells are seen in the ovaries of newborn mice and E20.5, but not E18.5, indicating that tumor growth begins perinatally
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• females develop ovarian granulosa cell bilateral tumors with 100% penetrance from an early age
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• seminiferous tubule degeneration is seen by 3 weeks of age
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• 100% penetrance of aggressive testicular cancer
• tumors are first observable at 5 weeks of age, and by 3 months of age, about 70% of mice have unilateral testicular tumors and 30% have bilateral tumors
• tumors exhibit characteristics of granulosa cell tumors of the testis and not Sertoli cell tumors
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• presence of nests of dysplastic cells are seen in the ovaries of newborn mice and E20.5, but not E18.5, indicating that tumor growth begins perinatally
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• females develop ovarian granulosa cell bilateral tumors with 100% penetrance from an early age
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• seminiferous tubule degeneration is seen by 3 weeks of age
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• 100% penetrance of aggressive testicular cancer
• tumors are first observable at 5 weeks of age, and by 3 months of age, about 70% of mice have unilateral testicular tumors and 30% have bilateral tumors
• tumors exhibit characteristics of granulosa cell tumors of the testis and not Sertoli cell tumors
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• pulmonary tumor cell embolisms
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• extrensive extramedullary hematopoiesis
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• female mice die before 9 weeks of age
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• pulmonary tumor cell embolisms
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| granulosa cell tumor | DOID:2999 | J:142150 | ||
| testicular granulosa cell tumor | DOID:5331 | J:149060 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• female mutants develop granulosa cell tumors by 3 weeks of age
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• male mutants develop testicular granulosa cell tumors by 5 weeks of age
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• female mutants develop granulosa cell tumors by 3 weeks of age
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• male mutants develop testicular granulosa cell tumors by 5 weeks of age
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• female mutants develop granulosa cell tumors by 3 weeks of age
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• male mutants develop testicular granulosa cell tumors by 5 weeks of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| granulosa cell tumor | DOID:2999 | J:186144 | ||
| juvenile type testicular granulosa cell tumor | DOID:6032 | J:186144 | ||
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:186144 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• female mutants develop granulosa cell tumors by 12-14 weeks of age
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• male mutants develop granulosa cell tumors of the testis by 4-5 months of age; tumors do not spread or metastasize
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• female mutants develop granulosa cell tumors by 12-14 weeks of age
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• seminiferous tubule degeneration is seen by 4 weeks of age
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• male mutants develop granulosa cell tumors of the testis by 4-5 months of age; tumors do not spread or metastasize
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• female mutants develop granulosa cell tumors by 12-14 weeks of age
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• seminiferous tubule degeneration is seen by 4 weeks of age
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• male mutants develop granulosa cell tumors of the testis by 4-5 months of age; tumors do not spread or metastasize
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| granulosa cell tumor | DOID:2999 | J:186144 | ||
| juvenile type testicular granulosa cell tumor | DOID:6032 | J:186144 | ||
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:186144 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• all mutants die within 2-3 months of age due to tumor burden
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• mutants exhibit precancerous lesions in the ovaries by 3 weeks of age
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• mutants develop large granulosa cell tumors by 6-8 weeks of age
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• granulosa cell apoptosis is decreased in the ovaries at 5-6 weeks of age
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• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked
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• granulosa cell proliferation is increased in the ovaries at 5-6 weeks of age
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• mutants exhibit precancerous lesions in the ovaries by 3 weeks of age
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• mutants develop large granulosa cell tumors by 6-8 weeks of age
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• granulosa cell apoptosis is decreased in the ovaries at 5-6 weeks of age
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• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked
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• granulosa cell proliferation is increased in the ovaries at 5-6 weeks of age
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• mutants exhibit precancerous lesions in the ovaries by 3 weeks of age
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• mutants develop large granulosa cell tumors by 6-8 weeks of age
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• by 6 weeks of age
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• by 6 weeks of age
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• by 6 weeks of age
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• by 6 weeks of age
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• granulosa cell apoptosis is decreased in the ovaries at 5-6 weeks of age
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• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked
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• granulosa cell proliferation is increased in the ovaries at 5-6 weeks of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| granulosa cell tumor | DOID:2999 | J:186144 | ||
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:186144 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants die within 3.5-5.5 months of age
|
|
|
• female mutants exhibit precancerous lesions in the ovaries at between 4 and 5 weeks of age
|
|
|
• female mutants develop bilateral granulosa cell tumors by 3 months of age
|
|
|
• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked
|
|
|
• female mutants exhibit precancerous lesions in the ovaries at between 4 and 5 weeks of age
|
|
|
• female mutants develop bilateral granulosa cell tumors by 3 months of age
|
|
|
• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked
|
|
|
• female mutants exhibit precancerous lesions in the ovaries at between 4 and 5 weeks of age
|
|
|
• female mutants develop bilateral granulosa cell tumors by 3 months of age
|
|
|
• at 6 weeks of age in females
|
|
|
• at 6 weeks of age in females
|
|
|
• at 6 weeks of age in females
|
|
|
• at 6 weeks of age in females
|
|
|
• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| granulosa cell tumor | DOID:2999 | J:186144 | ||
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:186144 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival of 185 days and median survival of 200 days
|
|
• mice rapidly develop bladder tumors resembling urothelial cell carcinoma
|
|
• mice rapidly develop bladder tumors resembling urothelial cell carcinoma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| urinary bladder cancer | DOID:11054 |
OMIM:109800 |
J:234236 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop urothelial bladder tumors that progress to papillary carcinoma
|
|
• mice develop urothelial bladder tumors that progress to papillary carcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop urothelial bladder tumors that progress to papillary carcinoma
|
|
• mice develop urothelial bladder tumors that progress to papillary carcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• female tamoxifen-treated mice exhibit well-developed prepuce unlike wild-type female mice
• adult tamoxifen-treated mice exhibit a hyperplasic prepuce with enlarged external genitalia similar to male mice unlike wild-type female mice
• however, the scrotal/perineal region is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen administration leads to death of the mouse within 90 days from small intestine carcinoma
|
|
• two days after tamoxifen administration, there is a marked expansion of YFP+ cells within the crypts of the small intestine
• cultures of these cells yields four times as many, and much larger, clonogenic colonies
• ten days after tamoxifen administration, small intestine crypts are markedly disorganized with contiguous streams of YFP+ flowing out to the villi and forming a carpet of hyperplastic and grossly dysplastic cells
• sixty days after tamoxifen administration, the small intestine is twice the normal width and has a thickened, rugous appearance
• high-grade intraepithelial neoplasia and crypt adenoma formation is observed at the microscopic level sixty days after tamoxifen administration
• all mice die from the intestinal adenocarcinoma within 90 days of tamoxifen administration
|
|
• two days after tamoxifen administration, there is a marked expansion of YFP+ cells within the crypts of the small intestine
• cultures of these cells yields four times as many, and much larger, clonogenic colonies
• ten days after tamoxifen administration, small intestine crypts are markedly disorganized with contiguous streams of YFP+ flowing out to the villi and forming a carpet of hyperplastic and grossly dysplastic cells
• sixty days after tamoxifen administration, the small intestine is twice the normal width and has a thickened, rugous appearance
• high-grade intraepithelial neoplasia and crypt adenoma formation is observed at the microscopic level sixty days after tamoxifen administration
• all mice die from the intestinal adenocarcinoma within 90 days of tamoxifen administration
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival of 237 days and median survival of 238 days
|
|
• mice rapidly develop urothelial cell carcinoma
|
|
• mice rapidly develop urothelial cell carcinoma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| urinary bladder cancer | DOID:11054 |
OMIM:109800 |
J:234236 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• shorter survival due to lung cancer, with a survival time between 200-400 days
|
|
• 100% of mutants exhibit areas of hyperproliferation in the bladder urothelium from about 3 months of age, however these lesions do not progress further when examined at 12 months of age
|
| N |
• despite hyperproliferation in the bladder, mutants do not develop urothelial carcinoma by 12 months of age
• mutants do not develop skin papillomas
|
|
• 36% of mutants develop lung tumors by 1 year of age
• lung tumors resemble solitary fibrous tumors of the lugs (hemangiopericytomas)
|
|
• 36% of mutants develop lung tumors by 1 year of age
• lung tumors resemble solitary fibrous tumors of the lugs (hemangiopericytomas)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:174242 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• female mutants develop granulosa cell tumors by 6 months of age
|
|
|
• seminiferous tubule degeneration is seen by 5 weeks of age
|
|
|
• progressive loss of spermatogenesis and testicular atrophy with reduced testis size
|
|
|
• male mutants develop granulosa cell tumors of the testis by 9-13 weeks of age
|
|
|
• female mutants develop granulosa cell tumors by 6 months of age
|
|
|
• seminiferous tubule degeneration is seen by 5 weeks of age
|
|
|
• progressive loss of spermatogenesis and testicular atrophy with reduced testis size
|
|
|
• male mutants develop granulosa cell tumors of the testis by 9-13 weeks of age
|
|
|
• female mutants develop granulosa cell tumors by 6 months of age
|
|
|
• male mutants develop granulosa cell tumors of the testis by 9-13 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| granulosa cell tumor | DOID:2999 | J:186144 | ||
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:186144 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• majority of embryos die during early embryonic development due to extensive Beta-catenin activation
|
| N |
• female mice that survive to birth have a normal reproductive system without the masculinazation of genitalia normally associated with Rspo1 null mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following 4-hydroxytamoxifen (4-OHT) application, all mice develop melanoma over a 9 month period unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• died around 3 months of age of anemia and cachexia
|
|
• more than 3000 intestinal polyps/mouse by 3 weeks of age
• primarily in the duodenum and proximal jejunum
• lower densities in the ileum
• microadenomas in the colon
|
|
• more than 3000 intestinal polyps/mouse by 3 weeks of age
• primarily in the duodenum and proximal jejunum
• lower densities in the ileum
• microadenomas in the colon
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased proliferation of cells by E10
• 110% at E11 to 300% at E11.5
• E11 proliferation rate increased 1.4X
• 6.7% increase in progenitor cell death and apoptosis
• lower proportion of differentiated neurons to proliferative cells
|
|
• changes similar to those seen in the spinal cord
• tissue mass of the midbrain was increased
• increased proliferation in all areas of the brain
• progenitor domains of the midbrain and other areas of the brain increased
• increased apoptosis
|
|
• enlarged ventricular zone at E10.5
• increased area occupied by neural progenitor cells
• smaller area occupied by differentiated neurons (as determined immunohistochemically and by activity of genes expressed in progenitor cells)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in absence of lung formation, the pulmonary vascular plexus persists throughout embryonic development, but does not branch or develop further
|
|
• lungs fail to develop from the foregut
|
|
• lung agenesis is found in embryos examined at E13.5 and E17.5
|
| N |
• although no lungs develop, heart development and outflow and inflow tract structures are relatively normal, including atrial septation, septation between aorta and the pulmonary trunk, and atrioventricular canal development
|
|
• primitive non-branched pulmonary arteries which flank the esophagus and originate from the pulmonary trunk persist in E17.5 embryos
• pulmonary veins and pulmonary arteries develop and intersect at approximate location where a lung bud would be present in a normal embryo
|
|
• in absence of lung formation, the pulmonary vascular plexus persists throughout embryonic development, but does not branch or develop further
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• E13.5 tooth germs transplanted under the kidney capsule of adult mice for 3 weeks deposit little enamel matrix with premature differentiation of dental pulp cells and large amounts of dentin-like matrix unlike similarly treated wild-type tooth germs
• at E16.5, multiple epithelial invaginations are detected in the nasal side of the developing palatal shelves unlike in wild-type mice
• at E17.5 to P0, ectopic epithelial invaginations at the nasal side of the palatal shelves form morphologically distinct epithelial buds unlike in wild-type mice
• at birth, dental mesenchyme is abnormal
|
|
• at birth, dental mesenchyme is abnormal
|
|
• at birth, dental mesenchyme is abnormal
|
|
• E13.5 tooth germs transplanted under the kidney capsule of adult mice for 3 weeks deposit little enamel matrix with premature differentiation of dental pulp cells and large amounts of dentin-like matrix unlike similarly treated wild-type tooth germs
• at E16.5, multiple epithelial invaginations are detected in the nasal side of the developing palatal shelves unlike in wild-type mice
• at E17.5 to P0, ectopic epithelial invaginations at the nasal side of the palatal shelves form morphologically distinct epithelial buds unlike in wild-type mice
• at birth, dental mesenchyme is abnormal
|
|
• at birth, dental mesenchyme is abnormal
|
|
• E13.5 tooth germs transplanted under the kidney capsule of adult mice for 3 weeks deposit little enamel matrix with premature differentiation of dental pulp cells and large amounts of dentin-like matrix unlike similarly treated wild-type tooth germs
• at E16.5, multiple epithelial invaginations are detected in the nasal side of the developing palatal shelves unlike in wild-type mice
• at E17.5 to P0, ectopic epithelial invaginations at the nasal side of the palatal shelves form morphologically distinct epithelial buds unlike in wild-type mice
• at birth, dental mesenchyme is abnormal
|
|
• at birth, dental mesenchyme is abnormal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• died around E18.5; only 30% survived after birth
|
|
• endochondral bone elements all shorter
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• die by 4-5 weeks of age of unknown causes
|
|
• 200-700 intestinal polyps per mouse by 4 weeks of age
|
|
• 200-700 intestinal polyps per mouse by 4 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• with early gain-of-function mutation, at E9.5, initial organ commitment is normal, but by E13.5, there is complete absence of pituitary gland in all mutants
|
|
• with early gain-of-function mutation, at E9.5, initial organ commitment is normal, but by E13.5, there is complete absence of pituitary gland in all mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Kidney agenesis in Ctnnb1tm1Mmt/Ctnnb1+ Tg(Hoxb7-cre)13Amc/0 mice
|
• mice exhit both uni- and bilateral kidney agenesis, similar to that observed in Lrp4tm2Her homozygotes
• however, formation of the Wolffian duct and distal ureters as well as bladder and adrenal glands remain intact
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants die within 6-8 months of age
|
|
|
• ovaries exhibit visible precancerous lesions between 4 and 6 weeks of age and develop granulosa cell tumors
|
|
|
• ovaries exhibit visible precancerous lesions between 4 and 6 weeks of age and develop granulosa cell tumors
|
|
|
• ovaries exhibit visible precancerous lesions between 4 and 6 weeks of age and develop granulosa cell tumors
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:186144 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most embryos die between E12.5 and 16.5, likely due to vasculature defects
|
|
• most embryos die between E12.5 and 16.5, likely due to vasculature defects
|
|
• in some mutants this is turned downward and in others, is duplicated on the interior aspect
|
|
• mandibular prominences is increased in size, resulting in lack of proper lower jaw formation or fusion and forming a widened oral cavity
|
|
• maxillary prominence is increased in size, resulting in lack of proper upper jaw formation or fusion and forming a widened oral cavity
|
|
• the nasal process does not show controlled directional growth that results in formation of a normal nasal pit
|
|
• most mutants lack any recognizable facial features; some embryos have discernible features but these show severe defects
|
|
• embryos do not exhibit recognizable facial features except for a widened oral cavity
• facial development is normal at E9.0, but soon after facial prominences enlarge more rapidly than wild-type
• no significant changes in cell death or proliferation are detected at E10.5
|
|
• widened oral cavity
|
|
• at E12.5, mutants lack external (visible) ears
|
|
• in some mutants this is turned downward and in others, is duplicated on the interior aspect
|
|
• cartilages in the head such as the parachordal plate and cartilages of the ear are grossly malformed
• nasal cartilages are wider and misshapen
|
|
• mutants have extensive ectopic cartilages in the head region resulting in cartilage fusions and malformations
|
|
• at E12.5, mutants lack external (visible) ears
|
|
• at E12.5, mutants lack external eyes although rudimentary eyes are found internalized
|
|
• at E12.5, mutants lack vibrissae
|
|
• most mutants lack any recognizable facial features; some embryos have discernible features but these show severe defects
|
|
• embryos do not exhibit recognizable facial features except for a widened oral cavity
• facial development is normal at E9.0, but soon after facial prominences enlarge more rapidly than wild-type
• no significant changes in cell death or proliferation are detected at E10.5
|
|
• widened oral cavity
|
|
• at E12.5, mutants lack external (visible) ears
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal appendage development
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cranial muscle patterning and differentiation are abnormal as determined by marker expression
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 428 days
|
|
• keratinized squamous metaplasia of the preputial gland develops at 100 days (67% incidence), 200 days and at end-point (100% incidence)
|
|
|
• mice exhibit keratinized squamous metaplasia in the bulbourethral gland with incidence of 67% at 100 days and 100% at 200 days unlike wild-type mice
|
|
|
• at 200 days, mice develop adenocarcinoma foci
(J:143034)
• at end-point, 100% of mice develop diffuse and locally invasive adenocarcinoma unlike wild-type mice
(J:143034)
• prostatic tumor tissues show changes consistent with prostatic intracystic adenocarcinomas
(J:284956)
• 3 of 5 mice show intracystic adenocarcinoma at 6-9 months of age
(J:284956)
• 9 of 12 mice show intracystic adenocarcinoma at 9 months or older, with 1 of 12 showing invasive adenocarcinoma
(J:284956)
|
|
|
• at 100 days, mice exhibit diffuse prostate intraepithelial neoplasia-like keratinized squamous metaplasia unlike in wild-type mice
(J:143034)
• at 200 days, mice exhibit high-grade prostate intraepithelial neoplasia-like keratinized squamous metaplasia unlike in wild-type mice
(J:143034)
• mice develop PIN lesions starting at 4-6 weeks of age
(J:284956)
• 4 of 4 mice develop low grade PIN before 6 months of age and 3 of 4 mice show high grade PIN before 6 months of age
(J:284956)
• 5 of 5 mice develop high grade PIN at 6-9 months of age
(J:284956)
|
|
|
• at 200 days, mice develop adenocarcinoma foci
(J:143034)
• at end-point, 100% of mice develop diffuse and locally invasive adenocarcinoma unlike wild-type mice
(J:143034)
• prostatic tumor tissues show changes consistent with prostatic intracystic adenocarcinomas
(J:284956)
• 3 of 5 mice show intracystic adenocarcinoma at 6-9 months of age
(J:284956)
• 9 of 12 mice show intracystic adenocarcinoma at 9 months or older, with 1 of 12 showing invasive adenocarcinoma
(J:284956)
|
|
|
• at 100 days, mice exhibit diffuse prostate intraepithelial neoplasia-like keratinized squamous metaplasia unlike in wild-type mice
(J:143034)
• at 200 days, mice exhibit high-grade prostate intraepithelial neoplasia-like keratinized squamous metaplasia unlike in wild-type mice
(J:143034)
• mice develop PIN lesions starting at 4-6 weeks of age
(J:284956)
• 4 of 4 mice develop low grade PIN before 6 months of age and 3 of 4 mice show high grade PIN before 6 months of age
(J:284956)
• 5 of 5 mice develop high grade PIN at 6-9 months of age
(J:284956)
|
|
• urethral keratinized squamous metaplasia develops in 17% at day 200 and 28% at end-points unlike in wild-type mice
|
|
• keratinized squamous metaplasia of the preputial gland develops at 100 days (67% incidence), 200 days and at end-point (100% incidence)
|
|
|
• mice exhibit keratinized squamous metaplasia in the bulbourethral gland with incidence of 67% at 100 days and 100% at 200 days unlike wild-type mice
|
|
|
• at 200 days, mice develop adenocarcinoma foci
(J:143034)
• at end-point, 100% of mice develop diffuse and locally invasive adenocarcinoma unlike wild-type mice
(J:143034)
• prostatic tumor tissues show changes consistent with prostatic intracystic adenocarcinomas
(J:284956)
• 3 of 5 mice show intracystic adenocarcinoma at 6-9 months of age
(J:284956)
• 9 of 12 mice show intracystic adenocarcinoma at 9 months or older, with 1 of 12 showing invasive adenocarcinoma
(J:284956)
|
|
|
• at 100 days, mice exhibit diffuse prostate intraepithelial neoplasia-like keratinized squamous metaplasia unlike in wild-type mice
(J:143034)
• at 200 days, mice exhibit high-grade prostate intraepithelial neoplasia-like keratinized squamous metaplasia unlike in wild-type mice
(J:143034)
• mice develop PIN lesions starting at 4-6 weeks of age
(J:284956)
• 4 of 4 mice develop low grade PIN before 6 months of age and 3 of 4 mice show high grade PIN before 6 months of age
(J:284956)
• 5 of 5 mice develop high grade PIN at 6-9 months of age
(J:284956)
|
|
• urethral keratinized squamous metaplasia develops in 17% at day 200 and 28% at end-points unlike in wild-type mice
|
|
• keratinized squamous metaplasia of the preputial gland develops at 100 days (67% incidence), 200 days and at end-point (100% incidence)
|
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:143034 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• significantly reduced number of Gfra1+ undifferentiated spermatogonia in tubules
|
|
|
• significantly increased frequency of defective tubules (with lost or exiguous germ cell layer(s))
• significantly increased frequency of Sertoli cell only tubules
• significantly reduced number of Gfra1+ undifferentiated spermatogonia in tubules
|
|
|
• significantly reduced number of Gfra1+ undifferentiated spermatogonia in tubules
|
|
|
• significantly increased frequency of defective tubules (with lost or exiguous germ cell layer(s))
• significantly increased frequency of Sertoli cell only tubules
• significantly reduced number of Gfra1+ undifferentiated spermatogonia in tubules
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• normal number of Rarg+ undifferentiated spermatogonia in tubules
• significantly reduced number of Gfra1+ undifferentiated spermatogonia in tubules
|
|
|
• significantly increased frequency of defective tubules (with lost or exiguous germ cell layer(s))
• normal number of Rarg+ undifferentiated spermatogonia in tubules
• significantly reduced number of Gfra1+ undifferentiated spermatogonia in tubules
|
|
|
• normal number of Rarg+ undifferentiated spermatogonia in tubules
• significantly reduced number of Gfra1+ undifferentiated spermatogonia in tubules
|
|
|
• significantly increased frequency of defective tubules (with lost or exiguous germ cell layer(s))
• normal number of Rarg+ undifferentiated spermatogonia in tubules
• significantly reduced number of Gfra1+ undifferentiated spermatogonia in tubules
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal bone formation
|
|
• impaired
|
|
• impaired
|
|
• impaired
|
|
• impaired
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants die at birth
|
|
• from E14.5 - P0, examination shows that limbs are shorter than in wild-type
|
|
• expansion of Osx1 expression (Osx1-expressing cells) at E14.5, indicating promotion of osteoblast development, is observed
• no Oc+ terminal osteoblasts are found prior to E16.5, and few that are observed are restricted to periosteal region
|
|
• at E16.5, osteoclasts are absent from mutants when they are detected normally in wild-type
|
|
• at E14.5 and 16.5, tibia has abnormal wedge-shaped growth plate with few identifiable hypertrophic chondrocytes visible compared to wild-type
|
|
• at E16.5, no primary spongiosa-like matrix is observed in mutants, unlike wild-type; matrix resembles dense matrix restricted to region forming bone collar
|
|
• at E16.5, long bones appear to have a more intense and broader ossification center than in wild-type
• at P0, a thick bony matrix characterizes all long bones; bone formation is apparent in several cranial regions
• at E14.5, osteoblast lineage is expanded and 3-fold increase in proliferation of osteoblast-forming regions along the length of the periosteum
|
|
• at E14.5, extensive premature bone ossification of the tibia is seen, while no mineralization in wild-type has occurred
|
|
• delayed ossification in skull bones is apparent at E16.5
|
|
• at E16.5, osteoclasts are absent from mutants when they are detected normally in wild-type
|
|
• at E16.5, osteoclasts are absent from mutants when they are detected normally in wild-type
|
|
• expansion of Osx1 expression (Osx1-expressing cells) at E14.5, indicating promotion of osteoblast development, is observed
• no Oc+ terminal osteoblasts are found prior to E16.5, and few that are observed are restricted to periosteal region
|
|
• at E16.5, osteoclasts are absent from mutants when they are detected normally in wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• normal for the first two weeks after birth but die within a few days after weaning
|
|
• form but fail to erupt
|
|
• form but fail to erupt
|
|
• benign tumors in the ribs of 80% of mice
|
|
• benign tumors in the ribs of 80% of mice
|
|
• form but fail to erupt
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E15.5, lens epithelial cells accumulate posterior to the lens equator unlike in wild-type mice
• lens epithelial cells fail to exhibit the cell cycle
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop hyperplastic lesions in the bladder unlike wild-type mice
(J:164579)
• mice develop premalignant bladder lesions
(J:234236)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival of 231 days and median survival of 236 days
|
|
• mice rapidly develop bladder tumors with progression to non-invasive papillary carcinomas (urothelial cell carcinoma)
• the number of proliferating cells within each tumor is increased compared to single conditional Ctnnb1tm1Mmt homozygotes
• mice treated with a MEK1/2 inhibitor, PD184352, show tumor regression and reduction in proliferation
|
|
• mice rapidly develop bladder tumors with progression to non-invasive papillary carcinomas (urothelial cell carcinoma)
• the number of proliferating cells within each tumor is increased compared to single conditional Ctnnb1tm1Mmt homozygotes
• mice treated with a MEK1/2 inhibitor, PD184352, show tumor regression and reduction in proliferation
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| urinary bladder cancer | DOID:11054 |
OMIM:109800 |
J:234236 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop hyperplastic lesions in the bladder unlike wild-type mice
(J:164579)
• 100% of mutants exhibit areas of hyperproliferation in the bladder urothelium from about 3 months of age, however these lesions do not progress further when examined at 12 months of age
(J:174242)
|
| N |
• hyperproliferative lesions in the bladder do not progress to carcinoma
(J:164579)
• mutants aged up to 18 months do not develop lung tumors, skin tumors or urothelial carcinoma
(J:174242)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cystic index at P1 is increased compared to in Wnt9btm1.1Amc/Wnt9btm1.2Amc Tg(Cdh16-cre)91Igr mice
|
|
• cystic index at P1 is increased compared to in Wnt9btm1.1Amc/Wnt9btm1.2Amc Tg(Cdh16-cre)91Igr mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die by P2
|
|
• mild at birth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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 12/17/2024 MGI 6.24 |
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