Analysis Tools
neoplasm
|
• Background Sensitivity: spectrum of tumor incidence and onset on the BALB/c background are similar to Ptentm1.1Hwu on the BALB/c background in the first seven months
|
|
Allele Symbol Allele Name Allele ID |
Ptentm1Hwu targeted mutation 1, Hong Wu MGI:2156086 |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Summary |
159 genotypes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Background Sensitivity: spectrum of tumor incidence and onset on the BALB/c background are similar to Ptentm1.1Hwu on the BALB/c background in the first seven months
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• prostate adenocarcinoma is seen by 9-10 weeks of age in mutants infected with an adenovirus expressing Cre recombinase
|
|
|
• mutants infected with an adenovirus expressing Cre recombinase develop PIN by 7 weeks of age
|
|
• primary myotube cultures treated with adenovirus-cre to delete Pten results in increased myotube size
• primary myotube cultures treated with adenovirus-cre do not exhibit the palmitate-induced decrease in cell size seen in control myotubes
|
|
• mice injected neonatally with a cre-expressing adenovirus into the sensorimotor cortex and undergoing pyramidotomy in adulthood exhibit an increase in trans-midline sprouting of adult corticospinal tract axons compared to controls
• neonatal and postnatal deletion of Pten by injecting cre-expressing adenovirus into the sensorimotor cortex at the neonatal stage or 4 weeks of age, respectively, results in increased corticospinal tract regeneration following T8 complete spinal cord crush injury compared to controls
• the increase in corticospinal tract regeneration is seen when complete spinal cord crush is done at 2 and 5 months of age and the regenerating axons follow ectopic trajectories and extend bilaterally in contrast with normal unilateral extension in controls
• regenerating corticospinal tract axons after injury from mice injected with cre-expressing adenovirus are able to reform synaptic structures in the spinal cord caudal to the lesion site
|
|
|
• prostate adenocarcinoma is seen by 9-10 weeks of age in mutants infected with an adenovirus expressing Cre recombinase
|
|
|
• mutants infected with an adenovirus expressing Cre recombinase develop PIN by 7 weeks of age
|
|
|
• prostate adenocarcinoma is seen by 9-10 weeks of age in mutants infected with an adenovirus expressing Cre recombinase
|
|
|
• mutants infected with an adenovirus expressing Cre recombinase develop PIN by 7 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Defect in angioblast differentiation in Ptentm1Hwu/Ptentm1Hwu Kdrtm1Jrt/Kdr+ Twist2tm1.1(cre)Dor/Twist2+ mice
|
• vasculogenesis defect
• impaired differentiation of angioblasts into mature endothelial cells and blood vessels
|
|
• increase in angioblasts in E18.5 lungs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Increase in mesenchymal cell proliferation in Ptentm1Hwu/Ptentm1Hwu Twist2tm1.1(cre)Dor/Twist2+ mice
|
• lethality between E15.5 and E18.5
|
|
• mutants with less severe phenotypes die within 2-3 hours of birth, displaying cyanosis, chest retractions, and dyspnea
|
|
• increase in collagen deposition in the lungs
• alveolar spaces are frequently lined by cuboidal cells with immature lamellar bodies
|
|
• reduction in distal capillary network density in E15.5 lungs
• the capillary network is misaligned with corresponding respiratory airways (airway/capillary uncoupling or dysplasia) at E18.5
• increase in the distance between the capillaries and the lumen of the airways
|
|
• marker analysis indicates expansion of the distal epithelial progenitor cell domain
|
|
• E18.5 lungs exhibit a hypercellular mesenchymal compartment
• more than 5-fold increase in the number of CD45-CD31+ embryonic mesenchymal progenitor side population (E-SP) and CD45-CD31- E-SP cell populations in E17.5 lungs indicating an increase in lung mesenchymal progenitor cell populations
|
|
• in mutants with less severe phenotypes that die within hours of birth
|
|
• reduction in distal capillary network density in E15.5 lungs
• the capillary network is misaligned with corresponding respiratory airways (airway/capillary uncoupling or dysplasia) at E18.5
• increase in the distance between the capillaries and the lumen of the airways
|
|
• 44% of embryos lack of vascularization in entire embryos at E15.5
• E15.5 embryos show lack of vascularization in organs such as limbs and liver
• impaired differentiation of angioblasts into mature endothelial cells and blood vessels
|
|
• 15% of embryos exhibit hemorrhage at E18.5
|
|
• newborns show a decrease in blood oxygenation
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| persistent fetal circulation syndrome | DOID:13042 |
OMIM:265380 |
J:192736 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• accelerated oocyte growth
• many transient follicles contain degraded oocytes
|
|
|
• at P8, ovaries appear larger with more activated follicles
• by P23 and 35, ovaries remain larger and contain more activated follicles
|
|
|
• luteolysis is observed (degeneration of corpora lutea) at 12 weeks of age
|
|
|
• at P8, ovaries appear larger with more activated follicles, including transient follicles containing enlarged oocytes surrounded by flattened pregranulosa cells, primary follicles with enlarged oocytes surrounded by one layer of cuboidal granulosa cells and some secondary follicles with two layers of granulosa cells
• follicular structure at 12 weeks of age is deformed and luteolysis is observed
• reduction in follicle death and clearance before and around the time of sexual maturity
• at 7 weeks of age, ovaries show increased numbers of transient and preantral type 5 follicles
|
|
|
• growth dynamics of activated transient follicles is different than in controls, with some follicles remaining at the transient stage whereas others develop further
|
|
|
• premature activation of the primordial follicle pool resulting in depletion of primordial follicles in early adulthood
|
|
|
• percentage of primordial follicles in ovaries at P8 is lower (49.6%) than in controls (83.6%)
|
|
|
• by P23, no primordial follicles can be identified in mutants compared to 69.2% of follicles in controls areas are still at the primordial stage
|
|
|
• at P8, ovaries appear larger with more activated follicles
• by P23 and 35, ovaries remain larger and contain more activated follicles
|
|
|
• females exhibit activation of the pool of primordial follicles that leads to follicle depletion, causing premature ovarian failure
• many transient follicles contain degraded oocytes suggesting that some prematurely activated follicles undergo atresia
|
|
• increase in levels of follicle-stimulating hormone at 12-20-week old females
|
|
• increase in levels of luteinizing hormone at 12-20-week old females
|
|
|
• females exhibit activation of the pool of primordial follicles that leads to follicle depletion, causing premature ovarian failure
• many transient follicles contain degraded oocytes suggesting that some prematurely activated follicles undergo atresia
|
|
|
• accelerated oocyte growth
• many transient follicles contain degraded oocytes
|
|
|
• luteolysis is observed (degeneration of corpora lutea) at 12 weeks of age
|
|
|
• at P8, ovaries appear larger with more activated follicles, including transient follicles containing enlarged oocytes surrounded by flattened pregranulosa cells, primary follicles with enlarged oocytes surrounded by one layer of cuboidal granulosa cells and some secondary follicles with two layers of granulosa cells
• follicular structure at 12 weeks of age is deformed and luteolysis is observed
• reduction in follicle death and clearance before and around the time of sexual maturity
• at 7 weeks of age, ovaries show increased numbers of transient and preantral type 5 follicles
|
|
|
• growth dynamics of activated transient follicles is different than in controls, with some follicles remaining at the transient stage whereas others develop further
|
|
|
• premature activation of the primordial follicle pool resulting in depletion of primordial follicles in early adulthood
|
|
|
• percentage of primordial follicles in ovaries at P8 is lower (49.6%) than in controls (83.6%)
|
|
|
• by P23, no primordial follicles can be identified in mutants compared to 69.2% of follicles in controls areas are still at the primordial stage
|
|
|
• at P8, ovaries appear larger with more activated follicles
• by P23 and 35, ovaries remain larger and contain more activated follicles
|
|
|
• females exhibit activation of the pool of primordial follicles that leads to follicle depletion, causing premature ovarian failure
• many transient follicles contain degraded oocytes suggesting that some prematurely activated follicles undergo atresia
|
|
|
• older females exhibit irregular estrous cycles
|
|
|
• females become infertile in early adulthood, after 12-13 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• altered thyroid structure with normal areas that include colloid-filled follicles and normal areas with focal hyperplasia, polynuclear cells, small nonencapsulated areas of hypercellularity with solid and/or mircofollicular patterns and internal hemorrhage
|
|
• 100% of mutants develop differentiated follicular tumors of the thyroid after about 2 years of age
|
|
• P14 mutants show a mild decrease of T4 but normal TSH
|
|
• 100% of mutants develop differentiated follicular tumors of the thyroid after about 2 years of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| thyroid gland follicular carcinoma | DOID:3962 |
OMIM:188470 |
J:197590 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at P14, thyroid architecture is altered, with multilayered epithelial cells surrounding the colloid lumen and with some dysmorphic follicles containing abnormal material inside
|
|
• dysmorphic follicles containing abnormal material inside and multiple degenerative follicles which have varying degrees of colloid depletion are seen at P14
|
|
• increase in thyroid size is already seen at E15.5 and is striking by P14
|
|
• increase in epithelial cell proliferation rate at E15.5 and P14
• Background Sensitivity: at P14, epithelial cell proliferation rates are higher on the congenic C57BL/6 background than on the BALB/c background
|
|
• at P14, thyroid structure is completely altered with multiple degenerative follicles, which have varying degrees of colloid depletion, resembling a follicular adenoma
|
|
• increase in TSH at P14
|
|
• decrease in T4 hormonal levels at P14
|
|
• all mutants die before 2 weeks of age due to compression of the trachea and esophagus by the enlarged thyroid
|
|
• at P14, thyroid structure is completely altered with multiple degenerative follicles, which have varying degrees of colloid depletion, resembling a follicular adenoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Smaller body size of Ptentm1Hwu/Ptentm1Hwu Tg(Tyr-cre)1Lru/0 (HM) mice at P20
|
• die between 13 and 20 days after birth
|
|
• although mutants are similar in weight and size as wild-type mice on P2, they fail to gain as much weight over the next 20 days as controls
|
|
• mutants exhibit some intraluminal bubbles along the gastrointestinal tract
• mutants exhibit intestinal pseudoobstruction
|
|
• dilatation of the cecum
|
|
• mutants exhibit intestinal pseudoobstruction
|
|
• hypertrophy and hyperplasia of the myenteric and submucosal plexus in the enteric nervous system by 2 weeks of age resulting in ganglioneuromatosis
|
|
• enteric ganglia are bigger than in wild-type at P15
|
|
• hyperplasia is observed in enteric neuronal cells at E17.5 while hypertrophy of enteric neuronal cells is only seen after birth and not during embryonic development
|
|
• hyperpigmentation in the tail, pinna, paws, skin, and olfactory bulb
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| intestinal pseudo-obstruction | DOID:0080072 | J:155110 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal follicular development, showing healthy corpora lutea and preovulatory follicles at 16 weeks of age, normal resumption of meiosis, ovulation, fertilization and fertility, although PI3K-Akt signaling is elevated
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice injected intraperitoneally with poly(I:C) at P8 to induce loss of Pten all die at 20 to 35 days of age
|
|
• mice injected with poly(I:C) at P8 develop myeloproliferative neoplasm with clinical manifestations of Juvenile myelomonocytic leukemia at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 exhibit reduced total cell numbers in bone marrow at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 exhibit decreased hemoglobin 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 exhibit increased platelets 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show a reduction in lymphocytes 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show decreased B-cell (CD19+) populations in PB and spleen at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show decreased T-cell (CD3e+) populations in PB and spleen at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 exhibit a modest elevation in white blood cells 2-3 weeks post poly(I:C) treatment
|
|
• mice injected with poly(I:C) at P8 show an elevation in granulocytes in bone marrow, blood, and spleen 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 exhibit increased macrophages in bone marrow, blood, and spleen at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show an elevation in monocytes in bone marrow, blood, and spleen 2-3 weeks post induction
|
|
• bone marrow of mice injected with poly(I:C) at P8 shows decreased hematopoietic progenitor cells, including LIN-, LIN-Sca1-1-, cKit+, and LIN-Sca1-1+cKit+, are decreased, with less apoptosis
• spleen of mice injected with poly(I:C) at P8 shows an increase in hematopoietic progenitor cells
|
|
• mice injected with poly(I:C) at P8 show substantial monocyte/macrophage and granulocyte infiltration in the spleen at 2-3 weeks post induction
• spleen of mice injected with poly(I:C) at P8 shows an increase in hematopoietic progenitor cells
|
|
• mice injected with poly(I:C) at P8 exhibit increased spleen size
|
|
• mice injected with poly(I:C) at P8 exhibit increased spleen weight
|
|
• mice injected with poly(I:C) at P8 show a reduction in lymphocytes 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show decreased B-cell (CD19+) populations in PB and spleen at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show decreased T-cell (CD3e+) populations in PB and spleen at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 exhibit a modest elevation in white blood cells 2-3 weeks post poly(I:C) treatment
|
|
• mice injected with poly(I:C) at P8 show an elevation in granulocytes in bone marrow, blood, and spleen 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 exhibit increased macrophages in bone marrow, blood, and spleen at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show an elevation in monocytes in bone marrow, blood, and spleen 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show substantial monocyte/macrophage and granulocyte infiltration in the spleen at 2-3 weeks post induction
• spleen of mice injected with poly(I:C) at P8 shows an increase in hematopoietic progenitor cells
|
|
• mice injected with poly(I:C) at P8 exhibit increased spleen size
|
|
• mice injected with poly(I:C) at P8 exhibit increased spleen weight
|
|
• mice injected with poly(I:C) at P8 show substantial monocyte/macrophage infiltration in the liver at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 exhibit increased liver size
|
|
• mice injected with poly(I:C) at P8 exhibit increased liver weight
|
|
• mice injected with poly(I:C) at P8 develop myeloproliferative neoplasm with clinical manifestations of Juvenile myelomonocytic leukemia at 2-3 weeks post induction
• recipient mice transplanted with bone marrow nucleated cells from mutants develop an indolent myelodysplastic syndrome or myeloproliferative neoplasm by 8 weeks posttransplantation
• mice injected with poly(I:C) at 6 weeks of age develop a transient myeloproliferative neoplasm after 3 weeks post induction and 1/7 transform to T-ALL
|
|
• mice injected with poly(I:C) at 6 weeks of age develop a transient myeloproliferative neoplasm after 3 weeks post induction and 1/7 transform to T-ALL
|
|
• mice injected with poly(I:C) at P8 show substantial monocyte/macrophage infiltration in the spleens, livers, and lungs at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show increases in monocytes/macrophages and granulocytes in the bone marrow at 2-3 weeks post induction
• bone marrow of mice injected with poly(I:C) at P8 shows decreased hematopoietic progenitor cells, including LIN-, LIN-Sca1-1-, cKit+, and LIN-Sca1-1+cKit+, are decreased, with less apoptosis
|
|
• mice injected with poly(I:C) at P8 exhibit increased liver size
|
|
• mice injected with poly(I:C) at P8 exhibit increased liver weight
|
|
• mice injected with poly(I:C) at P8 exhibit increased spleen size
|
|
• mice injected with poly(I:C) at P8 exhibit increased spleen weight
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| juvenile myelomonocytic leukemia | DOID:0050458 |
OMIM:607785 |
J:232645 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival of poly(I:C) injected mice at P8 is 35 days
|
|
• mice injected with poly(I:C) at P8 exhibit increased spleen size
|
|
• mice injected with poly(I:C) at P8 exhibit increased spleen weight
|
|
• mice injected with poly(I:C) at P8 show an elevation in granulocytes 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 exhibit increased platelets 2-3 weeks post induction, although the level of platelet increase in smaller than in mice also heterozygous for Nf1tm1Fcr
|
|
• mice injected with poly(I:C) at P8 show a reduction in lymphocytes 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show decreased B-cell (CD19+) populations in PB and spleen at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show decreased T-cell (CD3e+) populations in PB and spleen at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show substantial macrophage infiltration in the spleens, livers, and lungs at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show an elevation in monocytes in the spleens, livers, and lungs at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 exhibit increased spleen size
|
|
• mice injected with poly(I:C) at P8 exhibit increased spleen weight
|
|
• mice injected with poly(I:C) at P8 show an elevation in granulocytes 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show a reduction in lymphocytes 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show decreased B-cell (CD19+) populations in PB and spleen at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show decreased T-cell (CD3e+) populations in PB and spleen at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show substantial macrophage infiltration in the spleens, livers, and lungs at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 show an elevation in monocytes in the spleens, livers, and lungs at 2-3 weeks post induction
|
|
• mice injected with poly(I:C) at P8 exhibit increased liver size
|
|
• mice injected with poly(I:C) at P8 exhibit increased liver weight
|
|
• mice injected with poly(I:C) at 6 weeks of age develop a transient myeloproliferative neoplasm after 3 weeks post induction and 5/7 transform to T-ALL
|
|
• mice injected with poly(I:C) at 6 weeks of age develop a transient myeloproliferative neoplasm after 3 weeks post induction and 5/7 transform to T-ALL
|
|
• mice injected with poly(I:C) at P8 exhibit increased liver weight
|
|
• mice injected with poly(I:C) at P8 exhibit increased spleen size
|
|
• mice injected with poly(I:C) at P8 exhibit increased spleen weight
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• invasive in 11 of 13 mice at 30 weeks of age
|
|
|
• high grade in 2 of 13 mice at 30 weeks of age
|
|
|
• invasive in 11 of 13 mice at 30 weeks of age
|
|
|
• high grade in 2 of 13 mice at 30 weeks of age
|
|
|
• invasive in 11 of 13 mice at 30 weeks of age
|
|
|
• high grade in 2 of 13 mice at 30 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants become ill shortly after pIpC treatment and exhibit lethargy, ruffling of fur, and hunched posture and die from leukemia
|
|
• mice treated with pIpC to induce Cre expression exhibit an enlarged thymus
|
|
• 10-fold increase in spleen cellularity after pIpC administration to induce Cre expression
|
|
• increase in blast cell frequency after pIpC administration to induce Cre expression
|
|
• mice treated with polyinosine-polycytidine (pIpC) to induce Cre expression exhibit extramedullary hematopoiesis, with prominent expansion in the number of immature myeloid cells
• mice develop myeloproliferative disease shortly after pIpC administration to induce Cre expression with complete effacement of the splenic architecture
|
|
• reduction in bone marrow cellularity after pIpC administration to induce Cre expression
|
|
• mice treated with pIpC to induce Cre expression exhibit an increase in hematopoietic stem cell proliferation but become depleted, most likely due to inhibition of self-renewal as no increase in cell death was observed
• mutants maintained on rapamycin after pIpC treatment do not exhibit expansion of hematopoietic stem cells
|
|
• mice treated with pIpC to induce Cre expression exhibit an enlarged thymus
|
|
• 10-fold increase in spleen cellularity after pIpC administration to induce Cre expression
|
|
• within 4-6 weeks after pIpC treatment, most mutants progress to leukemia, including acute myeloid leukemia and acute lymphoblastic leukemia
• mutants maintained on rapamycin after pIpC treatment do not develop leukemia
|
|
• seen in mutants within 4-6 weeks after pIpC treatment
|
|
• seen in mutants within 4-6 weeks after pIpC treatment
|
|
• mice treated with pIpC to induce Cre expression exhibit an enlarged thymus
|
|
• 10-fold increase in spleen cellularity after pIpC administration to induce Cre expression
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mutants do not develop hamartomas over a period of 300 days and epidermal thickness is normal at 8 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• expanded basal cell layers
|
|
• development of skin lesions is delayed and severity is reduced compared to single Pten mutants
|
|
• skin is thickened at 8 weeks of age, but to a lesser extent than in single Pten mutants
|
|
• develop skin hamartomas with a median latency of 121 days
|
|
• develop skin hamartomas with a median latency of 121 days
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• accumulation of terminally differentiated suprabasal cells
|
|
• development of skin lesions is delayed and severity is reduced compared to single Pten mutants
|
|
• skin is thickened at 8 weeks of age, but to a lesser extent than in single Pten mutants
|
|
• develop skin hamartomas with a median latency of 131 days
|
|
• develop skin hamartomas with a median latency of 131 days
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• marker analysis indicates a perturbed basal-to-suprabasal transition
|
|
• expanded suprabasal layer as indicated by an increase in Keratin 10-postive cells
|
|
• increase in the number of epidermal cell layers at 8 weeks of age
|
|
• progressive development of multiple dermal lesions after weaning
|
|
• at 8 weeks of age
|
|
• multiple cutaneous hamartomas are seen all over the body within 12 weeks of age
• median onset of disease is 62 days
• mice treated with BKM120, a pan-class I PI3K inhibitor, beginning at 3 weeks of age, do not develop PTEN hamartoma tumor syndrome skin lesions; removal of BKM120 results in development of lesions, indicating that continuous treatment is required
• mice with advanced multiple skin hamartomas treated with BKM120 show improved skin conditions
|
|
• papillomatous lesions around the facial orifices, ears, and paws, with most associated with hyperkeratosis
|
|
• multiple cutaneous hamartomas are seen all over the body within 12 weeks of age
• median onset of disease is 62 days
• mice treated with BKM120, a pan-class I PI3K inhibitor, beginning at 3 weeks of age, do not develop PTEN hamartoma tumor syndrome skin lesions; removal of BKM120 results in development of lesions, indicating that continuous treatment is required
• mice with advanced multiple skin hamartomas treated with BKM120 show improved skin conditions
|
|
• papillomatous lesions around the facial orifices, ears, and paws, with most associated with hyperkeratosis
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Cowden syndrome | DOID:6457 |
OMIM:PS158350 |
J:199362 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• death within 3 months of tamoxifen treatment
|
|
• small cell lung tumors 2.5 months after tamoxifen treatment
|
|
• increased proliferation of pulmonary neuroendocrine cells
|
|
• all mice develop thyroid tumors
|
|
• increased invasiveness at 2.5 months after tamoxifen treatment
|
|
• small cell lung tumors 2.5 months after tamoxifen treatment
|
|
• all mice develop thyroid tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most females that develop lymphomas die at about 9 weeks post-4OHT injection
• all mutants die from tumor burden by 45 weeks post-4OHT injection
|
|
• treatment of mice with 4OHT at 6 weeks of age to induce cre-mediated recombination results in tumor formation with a mean latency of 17 weeks
• multiple tumors are seen in 27.3% of 4OHT-treated mice
• 46.1% of females develop endometrial cancer after 4OHT treatment
|
|
|
• 35% of males develop intestinal cancer after 4OHT treatment, arising from the colorectum and small intestine
|
|
|
• 20% of males develop prostate cancer after 4OHT treatment
|
|
|
• prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment
|
|
• 76.9% incidence of lymphomas in females after 4OHT treatment
• 40% incidence of lymphomas in males after 4OHT treatment
• lymphomas mainly arise from the thymus and mesenteric lymph nodes
• all lymphomas are derived from CD3+ T-cells with either a mature appearance of small lymphocytes or large lymphoblasts
|
|
• about 50% of males and females exhibit malignant tumors at 21 weeks and 10-11 weeks after 4OHT treatment, respectively
|
|
• 10% of males and 15.4% of females develop squamous cell carcinoma of the epidermis after 4OHT treatment
|
|
• males develop small or large intestinal polyps at more than 35 weeks post 4OHT treatment
|
|
|
• 35% of males develop intestinal cancer after 4OHT treatment, arising from the colorectum and small intestine
|
|
|
• prostate hyperplasia is observed at 4-6 weeks post 4-OHT treatment
|
|
|
• 20% of males develop prostate cancer after 4OHT treatment
|
|
|
• prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment
|
|
• 76.9% incidence of lymphomas in females after 4OHT treatment
• 40% incidence of lymphomas in males after 4OHT treatment
• lymphomas mainly arise from the thymus and mesenteric lymph nodes
• all lymphomas are derived from CD3+ T-cells with either a mature appearance of small lymphocytes or large lymphoblasts
|
|
|
• prostate hyperplasia is observed at 4-6 weeks post 4-OHT treatment
|
|
|
• 20% of males develop prostate cancer after 4OHT treatment
|
|
|
• prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment
|
|
|
• most females develop endometrial hyperplasia at between 7 and 9 weeks post 4-OHT treatment
|
|
• 10% of males and 15.4% of females develop squamous cell carcinoma of the epidermis after 4OHT treatment
|
|
• about 50% of males and females exhibit malignant tumors at 21 weeks and 10-11 weeks after 4OHT treatment, respectively
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Tgfbr1tm1.1Karl/Tgfbr1tm1.1Karl Ptentm1Hwu/Ptentm1Hwu Tg(KRT14-cre/ERT)20Efu/0 mice develop anal squamous cell carcinoma
|
• tamoxifen treated mutants to induce cre-mediated deletion of Tgfbr1 and Pten develop head and neck tumors; papillomas progress to squamous cell carcinoma in the head and neck and oral cavity
(J:194652)
• treatment with rapamycin 2 weeks after tamoxifen administration delays initiation and reduces progression of papilloma and onset of squamous cell carcinoma
(J:194652)
• rapamycin treatment of mice with already established head and neck squamous cell carcinoma results in regression of those tumors; rapamycin decreases cell proliferation and increases apoptosis in these tumors
(J:194652)
• anal neoplasms that develop in tamoxifen treated mice originate from squamous epithelia and not from columnar epithelia, indicating squamous cell carcinoma
(J:209026)
• invasion into adjacent muscle tissue is seen in some mice
(J:209026)
• anal squamous cell carcinoma shows increased levels of proinflammatory cytokines
(J:209026)
• all mice develop head and neck squamous cell carcinomas 16 weeks after tamoxifen induction
(J:209026)
• rapamycin treatment 2 weeks after tamoxifen administration decreases cell proliferation, and delays and reduces the progression of anal squamous cell carcinoma
(J:209026)
|
|
• tamoxifen treated mutants to induce cre-mediated deletion of Tgfbr1 and Pten develop head and neck and oral cavity papillomas that progress to squamous cell carcinoma
|
|
• 33% of mice develop visible anal tumors in 6 weeks after tamoxifen treatment
|
|
• 4 weeks after oral tamoxifen treatment for 5 consecutive days, hyperplasia is seen in the perianal areas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| anal canal carcinoma | DOID:6126 |
OMIM:105580 |
J:209026 | |
| head and neck squamous cell carcinoma | DOID:5520 |
OMIM:275355 |
J:194652 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mutants develop tumors between 12 to 20 weeks, with 100% penetrance at 20 weeks
|
|
|
• all mice develop invasive adenocarcinoma in all prostate lobes
• malignant cells invade through the basement membrane into the adjacent stroma, inducing both an inflammatory and a desmoplastic response, resulting in growth of fibrous and connective tissue around the tumor
|
|
|
• mice develop prostate intraepithelial neoplasias
|
|
|
• mutants develop tumors between 12 to 20 weeks, with 100% penetrance at 20 weeks
|
|
|
• all mice develop invasive adenocarcinoma in all prostate lobes
• malignant cells invade through the basement membrane into the adjacent stroma, inducing both an inflammatory and a desmoplastic response, resulting in growth of fibrous and connective tissue around the tumor
|
|
|
• mice develop prostate intraepithelial neoplasias
|
|
|
• mutants develop tumors between 12 to 20 weeks, with 100% penetrance at 20 weeks
|
|
|
• all mice develop invasive adenocarcinoma in all prostate lobes
• malignant cells invade through the basement membrane into the adjacent stroma, inducing both an inflammatory and a desmoplastic response, resulting in growth of fibrous and connective tissue around the tumor
|
|
|
• mice develop prostate intraepithelial neoplasias
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mutants exhibit visible solid tumor mass with invasive adenocarcinoma in the anterior prostate, while the dorsolateral prostate and ventral prostate lobes keep their ductual structure, albeit with enlarged ducts
|
|
|
• dorsolateral prostate and ventral prostate exhibit diffusive prostate intraepithelial neoplasia (PIN) with intact basement membrane
|
|
|
• mutants exhibit visible solid tumor mass with invasive adenocarcinoma in the anterior prostate, while the dorsolateral prostate and ventral prostate lobes keep their ductual structure, albeit with enlarged ducts
|
|
|
• dorsolateral prostate and ventral prostate exhibit diffusive prostate intraepithelial neoplasia (PIN) with intact basement membrane
|
|
|
• mutants exhibit visible solid tumor mass with invasive adenocarcinoma in the anterior prostate, while the dorsolateral prostate and ventral prostate lobes keep their ductual structure, albeit with enlarged ducts
|
|
|
• dorsolateral prostate and ventral prostate exhibit diffusive prostate intraepithelial neoplasia (PIN) with intact basement membrane
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycyline treated mice exhibit an increase in proliferation of epithelial cells lining conducting airways
|
|
• papillary epithelial hyperplasia is seen as early as 4-6 weeks of age in mice treated with doxycycline
• papillary epithelial hyperplasia is characterized by a hypercellular epithelium lining papillae with fibrovascular cores that protrude into the airway lumens
|
|
• doxycyline treated mice exhibit an increase in proliferation of nonciliated bronchial and bronchiolar Clara cells
|
|
• mice treated with doxycycline exhibit bronchiolar epithelial hyperplasia, producing papillae composed of fibrovascular cores lined by a hypercellular epithelium protruding into the airway lumens consisting of enlarged cells
|
|
• mice treated with doxycycline exhibit bronchial epithelial hyperplasia, producing papillae composed of fibrovascular cores lined by a hypercellular epithelium protruding into the airway lumens consisting of enlarged cells
|
|
• pulmonary neuroepithelial cell hyperplasia, with a 2-fold increase in the number of pulmonary neuroendocrine cells in mice treated with doxycycline
• however normal respiratory epithelial cell differentiation and respiratory epithelial cell polarity
|
|
• pulmonary neuroepithelial cell hyperplasia, with a 2-fold increase in the number of pulmonary neuroendocrine cells in mice treated with doxycycline
• however normal respiratory epithelial cell differentiation and respiratory epithelial cell polarity
|
| N |
• overt pulmonary tumors are not observed in doxycycline treated mice at 6 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• impaired survival is seen beginning around 2 months of age
• death appears to result from excessive bleeding due to invasion of uterine blood vessels by tumor cells
|
|
|
• hyperplasia progresses to carcinoma by 3 weeks of age
|
|
|
• by P10, luminal and glandular epithelial hyperplasia are seen
|
|
|
• enlarged relative to conditional mutants that are wild type for Trp53
|
|
|
• hyperplasia progresses to carcinoma by 3 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| endometrial cancer | DOID:1380 |
OMIM:608089 |
J:139053 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice develop prostatic sarcomatoid carcinoma
• mice show a more aggressive prostatic tumor phenotype than single conditional Ptentm1Hwu mice
|
|
|
• mice develop prostatic adenocarcinomas and invasive carcinomas
|
|
|
• 5 of 5 mice develop multifocal high grade intraepithelial neoplasia (PIN) before 4 months of age
|
|
|
• mice develop prostatic sarcomatoid carcinoma
• mice show a more aggressive prostatic tumor phenotype than single conditional Ptentm1Hwu mice
|
|
|
• mice develop prostatic adenocarcinomas and invasive carcinomas
|
|
|
• 5 of 5 mice develop multifocal high grade intraepithelial neoplasia (PIN) before 4 months of age
|
|
|
• prostate cancer metastasis after 10 months of age with 62.5% of mice showing metastatic lesions
• metastasis to lungs and periprostatic lymph nodes is seen
• mice show an overall more invasive tumor phenotype than single conditional Ptentm1Hwu mice
|
|
|
• 1 of 5 mice show invasive pancreatic carcinoma at 4-10 months and 6 of 8 mice develop invasive carcinoma after 10 months of age; 5 of 8 mice have invasive carcinoma with epithelial-mesenchymal transition and 5 of 8 mice have invasive carcinoma with metastasis
• mice exhibit a transition from prostatic adenocarcinoma and invasive carcinoma lesions to pathology resembling prostatic sarcamoid carcinomas
• sarcamoid carcinomas show spindle-like tumor cells, tumor cells with a multitude of mitotic figures, and haphazard acini and lobules of pleomorphic cells, indicating that these lesions possess mesenchymal morphology and proliferative and invasive features
|
|
|
• mice develop prostatic sarcomatoid carcinoma
• mice show a more aggressive prostatic tumor phenotype than single conditional Ptentm1Hwu mice
|
|
|
• mice develop prostatic adenocarcinomas and invasive carcinomas
|
|
|
• 5 of 5 mice develop multifocal high grade intraepithelial neoplasia (PIN) before 4 months of age
|
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:268934 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• bone marrow cultured with IL-7 over a 6 day period to promote selective expansion of pre-B cells exhibits an approximate 7-fold enhancement in the frequency of activated immature mutant B cells relative to immature wild-type B cells
• gating on activated B cells shows that immature mutant B cells proliferate to a much greater extent than immature wild-type B cells
• these experiments show that upon BCR engagement, immature B cells are activated and proliferate rather than being inhibited and undergoing anergy
|
|
• increase in the absolute number of splenic B cells, attributed mainly to the expansion/accumulation of MZ B cells
|
|
• expansion of the B1 cell population
|
|
• expansion of the MZ B cell compartment
|
|
• increase in numbers of IgMhi antibody secreting cells and decrease in numbers of IgGhi antibody secreting cells
|
|
• reduction in germinal center formation in response to sheep red blood cell immunization and in response to environmental antigens
|
|
• B cells are responsive to chemotactic stimuli but show reduced directed movement toward the stimulus
|
|
• cultured B cells show increased apoptosis
|
|
• B cells are hyperproliferative in response to mitogenic stimuli and exhibit a lower threshold for activation through the B cell antigen receptor
(J:83213)
• B cells exhibit altered cell cycle progression, with an increase in the percentage of cells in S and G2-M stages
(J:83213)
• neonatal B cells proliferate strongly in response to both LPS and anti-IgM F(ab')2 unlike wild-type B cells which show a modest proliferation in response to LPS and no proliferation in response to the anti-IgM F(ab')2
(J:155314)
|
|
• impaired class-switch recombination in antibody secreting cells in response to a T-dependent antigen; B cells fail to undergo class-switch recombination to IgG3 or IgG1 in the presence of LPS or LPS plus IL-4, respectively
• however, well-formed germinal centers are observed in spleen after immunization
|
|
• decrease in IgG after TNP-OVA immunization
|
|
• increase in IgM after TNP-OVA immunization
|
|
• bone marrow cultured with IL-7 over a 6 day period to promote selective expansion of pre-B cells exhibits an approximate 7-fold enhancement in the frequency of activated immature mutant B cells relative to immature wild-type B cells
• gating on activated B cells shows that immature mutant B cells proliferate to a much greater extent than immature wild-type B cells
• these experiments show that upon BCR engagement, immature B cells are activated and proliferate rather than being inhibited and undergoing anergy
|
|
• increase in the absolute number of splenic B cells, attributed mainly to the expansion/accumulation of MZ B cells
|
|
• expansion of the B1 cell population
|
|
• expansion of the MZ B cell compartment
|
|
• increase in numbers of IgMhi antibody secreting cells and decrease in numbers of IgGhi antibody secreting cells
|
|
• reduction in germinal center formation in response to sheep red blood cell immunization and in response to environmental antigens
|
|
• B cells are responsive to chemotactic stimuli but show reduced directed movement toward the stimulus
|
|
• cultured B cells show increased apoptosis
|
|
• B cells are hyperproliferative in response to mitogenic stimuli and exhibit a lower threshold for activation through the B cell antigen receptor
(J:83213)
• B cells exhibit altered cell cycle progression, with an increase in the percentage of cells in S and G2-M stages
(J:83213)
• neonatal B cells proliferate strongly in response to both LPS and anti-IgM F(ab')2 unlike wild-type B cells which show a modest proliferation in response to LPS and no proliferation in response to the anti-IgM F(ab')2
(J:155314)
|
|
• impaired class-switch recombination in antibody secreting cells in response to a T-dependent antigen; B cells fail to undergo class-switch recombination to IgG3 or IgG1 in the presence of LPS or LPS plus IL-4, respectively
• however, well-formed germinal centers are observed in spleen after immunization
|
|
• decrease in IgG after TNP-OVA immunization
|
|
• increase in IgM after TNP-OVA immunization
|
|
• cultured B cells show increased apoptosis
|
|
• B cells are hyperproliferative in response to mitogenic stimuli and exhibit a lower threshold for activation through the B cell antigen receptor
(J:83213)
• B cells exhibit altered cell cycle progression, with an increase in the percentage of cells in S and G2-M stages
(J:83213)
• neonatal B cells proliferate strongly in response to both LPS and anti-IgM F(ab')2 unlike wild-type B cells which show a modest proliferation in response to LPS and no proliferation in response to the anti-IgM F(ab')2
(J:155314)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• the population of B1 and MZ B cells that are absent in single homozygous CD19 mutants is restored
• mutants are capable of forming germinal centers when immunized with sheep red blood cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• macrophage recruitment to inflamed lungs is increased
|
|
• number of resident alveolar macrophages in unchallenged mutants is increased by more than 60% percent compared to wild-type
|
|
• neutrophils isolated from bone marrow live longer than wild-type neutrophils
(J:114699)
• neutrophils exhibit enhanced ruffling in response to the chemoattractant fMLP or IL-8
(J:145331)
• polarized neutrophils exhibit a considerable increase in multiple pseudopodia compared to wild-type mice
(J:145331)
• neutrophils show more diffuse F-actin localization at the leading edge or pseudopodia than wild-type neutrophils
(J:145331)
• fMLP-stimulated, but not PMA-stimulated, neutrophils exhibit increased and prolonged superoxide production compared to wild-type neutrophils
(J:145331)
• neutrophils exhibit enhanced transwell chemotaxis toward fMLP, IL-8 or C5a
(J:145331)
• neutrophils are more active and move faster than wild-type neutrophils but lack some of the directionality of wild-type neutrophils
(J:145331)
• in a model of peritonitis, neutrophil recruitment at sites of inflammation is increased in mutants compared to wild-type mice
(J:145331)
• in a model of bacterial pneumonia, apoptosis of lung recruited neutrophils is reduced in mutants compared to wild-type mice
(J:148947)
• neutrophils exhibit enhanced bacteria-killing capacity in a model of bacterial pneumonia
(J:148947)
• neutrophils have an increased phagocytic index compared to wild-type in a model of bacterial pneumonia
(J:148947)
• neutrophils exhibit enhanced E.coli and zymosan-induced phagocytosis-associated superoxide production
(J:148947)
|
|
• in a bacterial pneumonia model in which mutants are intratracheally infected with E.coli to induce lung inflammation, mutants exhibit an increase in bacteria-induced neutrophil recruitment compared to controls
• mutants treated with the chemotherapeutic drug, cyclophosphamide, to induce neutropenia, exhibit fewer neutrophils in the lungs than untreated mutants, but more neutrophils than drug treated wild-type mice
|
|
• increase in cytokine/chemokine concentrations in inflamed lungs of E.coli infected mutants due to increased numbers of resident alveolar macrophages and not due to enhanced capability of macrophages to produce cytokines or chemokines
|
|
• mutants develop more severe lung inflammation in response to bacterial pneumonia than controls
|
|
• induction of neutropenia in mutants with the chemotherapeutic drug, cyclophosphamide, results in enhanced neutrophil accumulation in the lungs leading to better clearance of instilled bacteria and accelerated resolution of bacteria-induced lung inflammation
|
|
• mutants made neutropenic with the chemotherapeutic drug, cyclophosphamide, exhibit decreased mortality after E.coli challenge compared to wild-type mice due to enhanced neutrophil accumulation in the lungs (50% survival for mutants compared to 7% survival for wild-type mice)
|
|
• mutants intratracheally infected with E.coli exhibit increased neutrophil recruitment to lungs and increased lung inflammation, pulmonary edema, and increased susceptibility to death compared to controls
|
|
• mutants exhibit an increase in pneumonia-associated death rate compared to wild-type mice, with only 50% of mutants surviving compared to 80% survival of wild-type mice
|
|
• macrophage recruitment to inflamed lungs is increased
|
|
• number of resident alveolar macrophages in unchallenged mutants is increased by more than 60% percent compared to wild-type
|
|
• neutrophils isolated from bone marrow live longer than wild-type neutrophils
(J:114699)
• neutrophils exhibit enhanced ruffling in response to the chemoattractant fMLP or IL-8
(J:145331)
• polarized neutrophils exhibit a considerable increase in multiple pseudopodia compared to wild-type mice
(J:145331)
• neutrophils show more diffuse F-actin localization at the leading edge or pseudopodia than wild-type neutrophils
(J:145331)
• fMLP-stimulated, but not PMA-stimulated, neutrophils exhibit increased and prolonged superoxide production compared to wild-type neutrophils
(J:145331)
• neutrophils exhibit enhanced transwell chemotaxis toward fMLP, IL-8 or C5a
(J:145331)
• neutrophils are more active and move faster than wild-type neutrophils but lack some of the directionality of wild-type neutrophils
(J:145331)
• in a model of peritonitis, neutrophil recruitment at sites of inflammation is increased in mutants compared to wild-type mice
(J:145331)
• in a model of bacterial pneumonia, apoptosis of lung recruited neutrophils is reduced in mutants compared to wild-type mice
(J:148947)
• neutrophils exhibit enhanced bacteria-killing capacity in a model of bacterial pneumonia
(J:148947)
• neutrophils have an increased phagocytic index compared to wild-type in a model of bacterial pneumonia
(J:148947)
• neutrophils exhibit enhanced E.coli and zymosan-induced phagocytosis-associated superoxide production
(J:148947)
|
|
• in a bacterial pneumonia model in which mutants are intratracheally infected with E.coli to induce lung inflammation, mutants exhibit an increase in bacteria-induced neutrophil recruitment compared to controls
• mutants treated with the chemotherapeutic drug, cyclophosphamide, to induce neutropenia, exhibit fewer neutrophils in the lungs than untreated mutants, but more neutrophils than drug treated wild-type mice
|
|
• increased neutrophil recruitment to lungs leads to pulmonary edema formation and increased protein accumulation
|
|
• increase in cytokine/chemokine concentrations in inflamed lungs of E.coli infected mutants due to increased numbers of resident alveolar macrophages and not due to enhanced capability of macrophages to produce cytokines or chemokines
|
|
• mutants made neutropenic with the chemotherapeutic drug, cyclophosphamide, exhibit decreased mortality after E.coli challenge compared to wild-type mice due to enhanced neutrophil accumulation in the lungs (50% survival for mutants compared to 7% survival for wild-type mice)
|
|
• mutants exhibit an increase in pneumonia-associated death rate compared to wild-type mice, with only 50% of mutants surviving compared to 80% survival of wild-type mice
|
|
• number of resident alveolar macrophages in unchallenged mutants is increased by more than 60% percent compared to wild-type
|
|
• increased neutrophil recruitment to lungs leads to pulmonary edema formation and increased protein accumulation
|
|
• mutants develop more severe lung inflammation in response to bacterial pneumonia than controls
|
|
• macrophage recruitment to inflamed lungs is increased
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants exhibit a hunched posture by 4 months of age
|
|
• mutants exhibit weight loss by 4 months of age
|
|
• mutants exhibit splenomegaly by 4 months of age
|
|
• mutants exhibit splenomegaly by 4 months of age
|
|
• CD19+ B cells are larger than B cells from wild-type mice
• B cell neoplasia
|
|
• reduction in the frequency of B cells in asymptomatic double mutant mice as compared to controls or either single mutant mouse
|
|
• mutants older than 6 months of age have a 3-fold increase in the percentage of recirculating B cells in the blood, concurrent with onset of disease
|
|
• tissues containing the expanded B cell population also display an expansion of CD11b+ myeloid cells
|
|
• spleens of mutants over 6 months of age exhibit an expansion of CD19+ B cells, resulting in enlarged white pulp areas that often infiltrate and compress the red pulp
|
|
• B cells exhibit enhanced survival
|
|
• B cells proliferate to the prosurvival factor B cell activating factor (BAFF) while wild-type B cells do not
• B cells show a more robust proliferative response to LPS or anti-CD40 than wild-type mice
|
|
• mutants exhibit splenomegaly by 4 months of age
|
|
• B cell neoplasia
• CD19+ B cells are larger than B cells from wild-type mice
|
|
• reduction in the frequency of B cells in asymptomatic double mutant mice as compared to controls or either single mutant mouse
|
|
• mutants older than 6 months of age have a 3-fold increase in the percentage of recirculating B cells in the blood, concurrent with onset of disease
|
|
• tissues containing the expanded B cell population also display an expansion of CD11b+ myeloid cells
|
|
• spleens of mutants over 6 months of age exhibit an expansion of CD19+ B cells, resulting in enlarged white pulp areas that often infiltrate and compress the red pulp
|
|
• B cells exhibit enhanced survival
|
|
• B cells proliferate to the prosurvival factor B cell activating factor (BAFF) while wild-type B cells do not
• B cells show a more robust proliferative response to LPS or anti-CD40 than wild-type mice
|
|
• mutants exhibit ruffled fur by 4 months of age
|
|
• severe morbidity and death occurs in all mutants by 1 year of age
|
|
• mutants develop marginal zone lymphoma, and less frequently, follicular B cell lymphoma or centroblastic lymphoma
|
|
• mutants develop spontaneous and lethal mature B cell neoplasms consistent with marginal zone lymphoma
|
|
• lymphoma infiltrates are seen in nonlymphoid tissues, including liver, lung, heart, and kidney
|
|
• B cells proliferate to the prosurvival factor B cell activating factor (BAFF) while wild-type B cells do not
• B cells show a more robust proliferative response to LPS or anti-CD40 than wild-type mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| B-cell lymphoma | DOID:707 | J:166155 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mutants develop lethal prostate cancer 4 months after tamoxifen induction
|
|
|
• mutants develop lethal prostate cancer 4 months after tamoxifen induction
• tumors are large and highly proliferative and are primarily composed of luminal epithelial cells
• tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration
• tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative
• treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation
|
|
|
• tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction
|
|
|
• tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction
|
|
|
• metastases to lungs and lymph nodes are seen in tamoxifen treated mutants and disseminated tumor cells are seen in the bone marrow
|
|
|
• mutants develop lethal prostate cancer 4 months after tamoxifen induction
• tumors are large and highly proliferative and are primarily composed of luminal epithelial cells
• tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration
• tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative
• treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation
|
|
|
• tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction
|
|
|
• tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction
|
|
|
• mutants develop lethal prostate cancer 4 months after tamoxifen induction
• tumors are large and highly proliferative and are primarily composed of luminal epithelial cells
• tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration
• tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative
• treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation
|
|
|
• tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction
|
|
|
• tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| prostate cancer | DOID:10283 |
OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959 |
J:191327 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 70% of mice develop granulosa-cell tumors in the ovary
|
|
|
• 30% of mice develop high-grade serous carcinoma originating in the ovary
• however, mice do not develop serous carcinomas originating from the fallopian tube
|
|
|
• serous carcinoma spreads throughout the peritoneal cavity, to the omentum and across the peritoneal membrane, including the mesentery and diaphragm
|
|
|
• median survival is 11.2 months of age, with mice dying between 7.6 and 15.3 months of age
|
|
|
• 70% of mice develop granulosa-cell tumors in the ovary
|
|
|
• 30% of mice develop high-grade serous carcinoma originating in the ovary
• however, mice do not develop serous carcinomas originating from the fallopian tube
|
|
|
• 70% of mice develop granulosa-cell tumors in the ovary
|
|
|
• 30% of mice develop high-grade serous carcinoma originating in the ovary
• however, mice do not develop serous carcinomas originating from the fallopian tube
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:222579 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice show widespread peritoneal metastases, including omentum and diaphragm
• the overall metastatic tumor burden in fallopian tube-removed mice is less extensive than that of intact mice
|
|
|
• mice develop massive high-grade serous carcinomas that always arise from the fallopian tube
• however when fallopian tubes are removed, mice develop high-grade serous carcinomas originating from the ovary, indicating that the ovary can be a source of carcinomas but is less dominant in tumorigenesis than the fallopian tube
|
|
|
• ovary has on overgrowth of tumors composed of cells showing nuclear pleiomprhism, irregular chromatin distribution, macronucleoli, increased mitotic activity and widespread apoptosis resembling high-grade human serous ovarian cancer
|
|
|
• premature death starting around 6 months of age with all mice dying by around 8 months of age
• fallopian tube-removed mice die at around 8-14 months of age after inducing ascites
|
|
|
• ovary has on overgrowth of tumors composed of cells showing nuclear pleiomprhism, irregular chromatin distribution, macronucleoli, increased mitotic activity and widespread apoptosis resembling high-grade human serous ovarian cancer
|
|
|
• ovary has on overgrowth of tumors composed of cells showing nuclear pleiomprhism, irregular chromatin distribution, macronucleoli, increased mitotic activity and widespread apoptosis resembling high-grade human serous ovarian cancer
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:222579 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• fallopian tube cancers subsequently spread to envelop the ovaries and then aggressively metastasize throughout the abdominal cavity, including the mesentery and pancreas, with prominent cancer lesions on the diaphragm and peritoneal membrane
|
|
|
• females develop early high-grade serous carcinomas in the fallopian tube
|
|
|
• tumors are characterized by complex papillae and glands forming slit-like spaces nad solid sheets of tumor cells with pleomorphic nuclei, prominent nucleoli, and high mitotic activity, resembling high-grade human serous ovarian cancer
• origin of the serous carcinomas, however is the fallopian tube
|
|
|
• after developing ascites, 100% of females die from the metastatic cancers between 6.5 and 13 months of age
|
|
|
• tumors are characterized by complex papillae and glands forming slit-like spaces nad solid sheets of tumor cells with pleomorphic nuclei, prominent nucleoli, and high mitotic activity, resembling high-grade human serous ovarian cancer
• origin of the serous carcinomas, however is the fallopian tube
|
|
|
• abnormal proliferation begins in the stromal compartment, not in the epithelial layer, of the fallopian tube; tumor cells in the stroma express epithelial markers indicating that stromal cells in the fallopian tube undergo a transition to an epithelial cell type during carcinoma formation
|
|
|
• tumors are characterized by complex papillae and glands forming slit-like spaces nad solid sheets of tumor cells with pleomorphic nuclei, prominent nucleoli, and high mitotic activity, resembling high-grade human serous ovarian cancer
• origin of the serous carcinomas, however is the fallopian tube
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:182161 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• failed tolerance induction resulting in abundant autoantibody production, indicating that B cells are prevented from acquiring an anergic state
• B cells have about 10 fold lower bound HEL than in mutants with intact Pten, suggesting that receptor occupancy is reduced on mutant autoreactive B cells and that less HEL is available in adults for inducing and sustaining anergy
• increasing the concentration of free self-antigen confers an anergic phenotype on mutant B cells, but they remain long-lived
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice injected with pIpC to induce Pten deletion have an enlarged thymus
|
|
• mice injected with pIpC to induce Pten deletion have an enlarged spleen
|
|
• mice injected with pIpC to induce Pten deletion, develop myeloproliferative disease and T-cell acute lymphoblastic leukemia, but at a slower rate than in single Pten mutants
|
|
• mean survival time of mice injected with pIpC to induce Pten deletion is 46 days
|
|
• mice injected with pIpC to induce Pten deletion have an enlarged thymus
|
|
• mice injected with pIpC to induce Pten deletion have an enlarged spleen
|
|
• mice injected with pIpC to induce Pten deletion have an enlarged thymus
|
|
• mice injected with pIpC to induce Pten deletion have an enlarged spleen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• about 25-30% increase in fasting glucose levels at 1 month of age
|
|
• glucose intolerance
|
| N |
• the liver phenotype observed in single Pten mutants is significantly reduced, with liver weights, triglyceride levels in the liver and fatty liver almost similar to controls
|
|
|
• progenitor cell accumulation in the periductal region of livers occurs later than in single conditional Pten homozygotes, when injury conditions are already present
|
|
|
• mice do not show development of steatosis compared to single conditional Pten homozygotes
|
|
|
• mice exhibit a 6-month delay in liver tumor onset compared to conditional Pten homozygotes
• no mice develop liver tumors between 9 and 12 months of age and 25% of mice older than 12 months develop liver nodules
• however, treatment of 3 month old mice with 3,5-dietoxycarbonyl-1,4 dihydrocollidine (DDC) to induce liver injury leads to massive expansion of hepatic progenitors and development of premalignant lesions
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice treated with an adenovirus expressing cre die by 6 months of age
|
|
• urinary bladder tumors in Adeno-cre treated mice are of epithelial origins and exhibit features of carcinoma in situ and high-grade invasive carcinoma with areas of transitional cell, squamous, and sarcomatoid carcinoma
|
|
• by 6 months, all mice treated with an adenovirus expressing cre (Adeno-cre) develop large urinary bladder tumors unlike wild-type mice
• by 4 to 6 months, 60% of Adeno-cre treated mice exhibit metastasis in the local lymph nodes, spleen, liver, and diaphragm
• however, treatment of mice with rapamycin following Adeno-cre injection prevents urinary bladder tumor formation
|
|
• by 6 months, all mice treated with an adenovirus expressing cre (Adeno-cre) develop large urinary bladder tumors unlike wild-type mice
• by 4 to 6 months, 60% of Adeno-cre treated mice exhibit metastasis in the local lymph nodes, spleen, liver, and diaphragm
• however, treatment of mice with rapamycin following Adeno-cre injection prevents urinary bladder tumor formation
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| urinary bladder cancer | DOID:11054 |
OMIM:109800 |
J:146760 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most die as early as 10 weeks of age, and usually within a week of showing signs of morbidity
|
|
• exaggerated startle response
|
|
• gliomas from asymptomatic mutants are primarily classified as grade 3 astocytomas
• 5-fold higher growth rate of astrocytomas compared with tumors from transgenic mice heterozygous for Nf1tm1Par and Trp53tm1Tyj and hemizygous for Tg(GFAP-cre)25Mes
|
|
• gliomas from asymptomatic mutants are primarily classified as grade 3 astocytomas
• 5-fold higher growth rate of astrocytomas compared with tumors from transgenic mice heterozygous for Nf1tm1Par and Trp53tm1Tyj and hemizygous for Tg(GFAP-cre)25Mes
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| malignant astrocytoma | DOID:3069 | J:134611 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants develop hyperplasia of the salivary glands later in life
|
|
• mutants develop hyperplasia of the salivary glands later in life
|
|
• increase in white matter volume
• progressive enlargement of all white matter tracts
|
|
• myelinated axons of the corpus callosum that intermingle with glial cells are in disarray
• density of myelinated axons in the ventral corpus callosum is decreased by 36.6% at 3 months of age
|
|
• oligodendroglial hypertrophy is seen at 4 months of age
|
|
• increase in numbers of myelinating and nonmyelinating Schwann cells
|
|
• increase in myelin sheath thickness
|
|
• sciatic nerves are increased in size
• myelinated axons are more loosely spaced in sciatic nerves
• number of myelinated axons in the sciatic nerve is higher at 3 months of age; increase in myelination is primarily for small caliber axons
|
|
• hypermyelination in both white and gray matter
• hypermyelination is primarily a consequence of additional membrane wraps and not by altered ultrastructure
• increase in myelin thickness is seen for axons of all calibers, however not all fibers are visibly hypermyelinated
• however, do not see ectopic myelination of CNS axons that normally are unmyelinated
• normally nonmyelinated C-fiber axons are spirally enwrapped by Remak Schwann cells; up to 10 membrane layers per axon are seen resulting in non compacted myelin
• Remak Schwann cells also ensheath bundles of collagen fibrils
• myelin outfoldings of variable length and aberrant myelin depositions are seen in the corpus callosum
|
|
• poor breeding
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival time of double mutants is shorter than either single mutant, with mice dying by 16 weeks of age
|
|
|
• development of endometrial cancer is accelerated compared to either single mutant
|
|
|
• decrease in the number of apoptotic cells in the endothelium epithelium compared to single Pten mutants
• proliferation is increased in the endothelium epithelium
|
|
|
• mutants exhibit endometrial hyperplasia at 2 weeks of age and develop endometrial adenocarcinoma at 4 weeks of age
• however, myometrial hyperplasia is not observed in the uteri of mutants
|
|
|
• increase in uterine weight at 2 weeks of age, with weight at 4 weeks greater than in single Pten mutants
|
|
• mutants exhibit distant metastases into the ovary, diaphragmatic skeletal muscle, lymph node, colon and pancreas
|
|
|
• development of endometrial cancer is accelerated compared to either single mutant
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| endometrial cancer | DOID:1380 |
OMIM:608089 |
J:162027 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are viable and exhibit not visible abnormalities and remain healthy throughout 12 months of study, with normal lungs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• 4 weeks after tamoxifen injections to induce Cre expression, pancreata exhibit no ductal metaplasia
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice display a progressive decline in survival due to the development of endometrial cancer; all mice die by ~50 weeks of age
|
|
|
• mice develop endometrial adenocarcinoma with invasion into the myometrium at 2 months of age
(J:162027)
• mice develop endometrial adenocarcinoma at 2 and 3 months of ages as characterized by neoplastic endometrial glands invading through the myometrium
(J:218222)
• treatment with U0126, an effective inhibitor of MAPK/ERK kinase, suppresses endometrial cancer progression, as shown by the arrest of tumors at the hyperplastic or normal stage
(J:218222)
|
|
|
• mice exhibit endometrial hyperplasia at 4 weeks of age
|
|
|
• mice treated with U0126, an effective inhibitor of MAPK/ERK kinase, display a significant decrease in uterine weight relative to mice treated with vehicle
|
|
|
• increase in uterine weight at 2 weeks of age
(J:162027)
• at 3 months of age, mice show a significant increase in uterine/body weight ratio relative to controls
(J:218222)
|
|
|
• proliferation is increased in the endothelium epithelium
|
|
|
• mice develop endometrial adenocarcinoma with invasion into the myometrium at 2 months of age
(J:162027)
• mice develop endometrial adenocarcinoma at 2 and 3 months of ages as characterized by neoplastic endometrial glands invading through the myometrium
(J:218222)
• treatment with U0126, an effective inhibitor of MAPK/ERK kinase, suppresses endometrial cancer progression, as shown by the arrest of tumors at the hyperplastic or normal stage
(J:218222)
|
|
|
• mice develop vaginal papillomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival is 8 weeks
|
|
• increase in inflammation in lesions compared to single Kras mutants, with an increase in neutrophil and endothelial cell infiltration; infiltration of these cells increases with malignant progression
|
|
• increase in inflammation in lesions compared to single Kras mutants, with an increase in neutrophil and endothelial cell infiltration; infiltration of these cells increases with malignant progression
|
|
• mutants have higher numbers of lesions and more extensive tumors than single Kras mutants
• mutants develop distinct bronchial and alveolar tumors
|
|
• mutants develop lung lesions as early as 4 weeks of age including proliferative atypical adenomatous hyperplasia lesions
|
|
• mutants develop lung lesions as early as 4 weeks of age that includes atypical papillary bronchiolar proliferation
|
|
• mucinous bronchioloalveolar cell carcinoma-like lesions, a subtype of lung adenocarcinoma
|
|
• mutants have higher numbers of lesions and more extensive tumors than single Kras mutants
• mutants develop distinct bronchial and alveolar tumors
|
|
• mutants develop lung lesions as early as 4 weeks of age including proliferative atypical adenomatous hyperplasia lesions
|
|
• mutants develop lung lesions as early as 4 weeks of age that includes atypical papillary bronchiolar proliferation
|
|
• mucinous bronchioloalveolar cell carcinoma-like lesions, a subtype of lung adenocarcinoma
|
|
• by 2 months of age, mutants exhibit weight loss
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• die before P68 with vascular complications
|
|
• 100% of mutants develop myeloproliferative disorder at about P30
|
|
• mutants exhibit vascular complication
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice exhibit significantly increased survival time relative to mice that are homozygous for Ptentm1Hwu and heterozygous for Pgrtm2(cre)Lyd, with >50% of mice still viable at 64 weeks of age
• mice do not die due to the development of endometrial cancer
|
|
|
• mice exhibit endometrial hyperplasia at 2 months but not at 3 months of age
• however, endometrial adenocarcinoma with invasion into the myometrium is not observed due to inhibition of ERK1/2 phosphorylation
|
|
|
• at 3 months of age, mice show a significantly reduced increase in uterine/body weight ratio relative to mice that are homozygous for Ptentm1Hwu and heterozygous for Pgrtm2(cre)Lyd
|
|
|
• at 2 months of age, mice show a significantly reduced uterine epithelial cell proliferation relative to mice that are homozygous for Ptentm1Hwu and heterozygous for Pgrtm2(cre)Lyd
|
|
|
• mice develop vaginal papillomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• impaired survival is seen beginning around 5 months of age
|
|
|
• hyperplasia progresses to carcinoma by 1 month of age with invasion into the myometrium detected by 3 months of age
|
|
|
• by P10, luminal and glandular epithelial hyperplasia are seen
|
|
|
• hyperplasia progresses to carcinoma by 1 month of age with invasion into the myometrium detected by 3 months of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| endometrial cancer | DOID:1380 |
OMIM:608089 |
J:139053 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mutants develop adenocarcinoma in the dorsolateral lobes of the prostate
• cancer progression is similar to single conditional Pten mice
• proliferation and apoptotic indexes are increased in the cancers, most notably in the proximal regions of the dorsal-lateral lobe
• mutant tumors contain low or no p63+ cells, similar to human prostate cancer
• castrated mutants develop cancer outgrowths in the dorsolateral lobes, indicating that mutants develop castrate-resistant prostate cancer
• castrated mice treated with rapamycin show a reduction in prostate volume and reduced prostate proliferation
|
|
|
• mutants develop adenocarcinoma in the dorsolateral lobes of the prostate
• cancer progression is similar to single conditional Pten mice
• proliferation and apoptotic indexes are increased in the cancers, most notably in the proximal regions of the dorsal-lateral lobe
• mutant tumors contain low or no p63+ cells, similar to human prostate cancer
• castrated mutants develop cancer outgrowths in the dorsolateral lobes, indicating that mutants develop castrate-resistant prostate cancer
• castrated mice treated with rapamycin show a reduction in prostate volume and reduced prostate proliferation
|
|
|
• mutants develop adenocarcinoma in the dorsolateral lobes of the prostate
• cancer progression is similar to single conditional Pten mice
• proliferation and apoptotic indexes are increased in the cancers, most notably in the proximal regions of the dorsal-lateral lobe
• mutant tumors contain low or no p63+ cells, similar to human prostate cancer
• castrated mutants develop cancer outgrowths in the dorsolateral lobes, indicating that mutants develop castrate-resistant prostate cancer
• castrated mice treated with rapamycin show a reduction in prostate volume and reduced prostate proliferation
|
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:172730 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 2.4 compared with 15.5 months
• 25% of tumors are adenomyoepitheliomas
• 25% of tumors are Erbb2 type neoplasms
• 25% of tumors exhibit squamous metaplasia and retention of myoepithelium
• 25% of tumors are glandular, composed of distinctive large cell population that are a signature phenotype of mammary tumors in these mice
• tumors are similar to HER2 and basal-like subtype of human breast cancer
|
|
• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 2.4 compared with 15.5 months
• 25% of tumors are adenomyoepitheliomas
• 25% of tumors are Erbb2 type neoplasms
• 25% of tumors exhibit squamous metaplasia and retention of myoepithelium
• 25% of tumors are glandular, composed of distinctive large cell population that are a signature phenotype of mammary tumors in these mice
• tumors are similar to HER2 and basal-like subtype of human breast cancer
|
|
• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 2.4 compared with 15.5 months
• 25% of tumors are adenomyoepitheliomas
• 25% of tumors are Erbb2 type neoplasms
• 25% of tumors exhibit squamous metaplasia and retention of myoepithelium
• 25% of tumors are glandular, composed of distinctive large cell population that are a signature phenotype of mammary tumors in these mice
• tumors are similar to HER2 and basal-like subtype of human breast cancer
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:133305 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 6.5 compared with 15.3 months
• tumor progression is associated with loss of heterozygosity at the Pten locus in 50% of mutant mammary tumors
• tumors are similar to basal-like subtype of human breast cancer
|
|
• 35% incidence of lung metastases compared with 5% in single Erbb2 mutants
|
|
• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 6.5 compared with 15.3 months
• tumor progression is associated with loss of heterozygosity at the Pten locus in 50% of mutant mammary tumors
• tumors are similar to basal-like subtype of human breast cancer
|
|
• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 6.5 compared with 15.3 months
• tumor progression is associated with loss of heterozygosity at the Pten locus in 50% of mutant mammary tumors
• tumors are similar to basal-like subtype of human breast cancer
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:133305 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most die as early as 10 weeks of age, and usually within a week of showing signs of morbidity
|
|
• exaggerated startle response
|
|
• mutants develop astrocytomas
• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci
|
|
• mutants develop astrocytomas
• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 20 to 28 weeks of age, mice exhibit increased germinal center B cell number compared to controls but not as much as in Gt(ROSA)26Sortm3Rsky/Gt(ROSA)26Sortm3Rsky/ Tg(CD2-cre)1Kio mice
|
|
• at 20 to 28 weeks of age, mice accumulate more antigen-experienced T cells than in control mice but not as much as in Gt(ROSA)26Sortm3Rsky/Gt(ROSA)26Sortm3Rsky/ Tg(CD2-cre)1Kio mice
|
|
• at 20 to 28 weeks of age, mice exhibit increased germinal center B cell number compared to controls but not as much as in Gt(ROSA)26Sortm3Rsky/Gt(ROSA)26Sortm3Rsky/ Tg(CD2-cre)1Kio mice
|
|
• at 20 to 28 weeks of age, mice accumulate more antigen-experienced T cells than in control mice but not as much as in Gt(ROSA)26Sortm3Rsky/Gt(ROSA)26Sortm3Rsky/ Tg(CD2-cre)1Kio mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• much thinner at age P21
|
|
• much thinner at age P21
|
|
• severe reduction at age P21
|
|
• severe reduction at age P21
|
|
• severe reduction at age P21
|
|
• much thinner at age P21
|
|
• much thinner at age P21
|
|
• much thinner at age P21
|
|
• much thinner at age P21
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 1 of 5 mutants develop a small acinar carcinoma
|
|
• 2 of 5 mutants develop papillary adenocarcionomas at 4 and 6 months of age
|
|
• 1 of 5 mutants develop a small acinar carcinoma
|
|
• 2 of 5 mutants develop papillary adenocarcionomas at 4 and 6 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• bladder urothelium exhibits increased cell proliferation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no differences in body weight and fat storage
|
|
• fasting mutants exhibit a 2.1-fold decrease in plasma insulin levels compared to controls indicating enhanced insulin sensitivity
|
|
• during a glucose tolerance test, mutants show a blunted elevation of blood glucose; the mean peak increase in blood glucose is 19% lower than that of controls
• mutants are protected from developing streptozotocin-induced diabetes; they maintain normal glycemia and remain resistant to the development of hyperglycemia
|
|
• mutants are more sensitive to insulin challenge (in insulin tolerance test), showing a 24% lower blood glucose at 60 min compared to wild-type mice
• insulin resistance is 1.9-fold lower for mutants than controls
|
|
• 36% lower serum concentrations of the adipocytokine resistin
|
|
• 36% lower serum concentrations of the adipocytokine resistin
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• in mice with two or more pregnancies
• however, virgin conditional mice do not develop breast cancer even after exposure to estrogen or progesterone and mice that do not breastfeed after more than 2 births fail to develop breast cancer
|
|
|
• in mice with two or more pregnancies
• however, virgin conditional mice do not develop breast cancer even after exposure to estrogen or progesterone and mice that do not breastfeed after more than 2 births fail to develop breast cancer
|
|
|
• in mice with two or more pregnancies
• however, virgin conditional mice do not develop breast cancer even after exposure to estrogen or progesterone and mice that do not breastfeed after more than 2 births fail to develop breast cancer
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• numbers of cleaved caspase 3 (CC3)-positive granulosa cells are decreased in eCG-primed mutant ovaries
|
|
|
• the increased numbers of corpora lutea are at different stages of differentiation than in controls
• steroid biosynthesis is similar in mutants as in controls indicating that even though life span of corpora lutea are extended, they do not remain steroidogenically active
|
|
|
• granulosa cells exhibit increased proliferation
|
|
|
• after 3 months of age, ovaries contain increased numbers of corpora lutea
|
|
|
• females exhibit increased follicle growth
• numbers of apoptotic follicles decreased in eCG-primed mutant ovaries
|
|
|
• after 3 months of age, ovaries are larger and contain increased numbers of corpora lutea
|
|
|
• after 3 months of age, ovaries are larger and contain increased numbers of corpora lutea
|
|
|
• numbers of cleaved caspase 3 (CC3)-positive granulosa cells are decreased in eCG-primed mutant ovaries
|
|
|
• the increased numbers of corpora lutea are at different stages of differentiation than in controls
• steroid biosynthesis is similar in mutants as in controls indicating that even though life span of corpora lutea are extended, they do not remain steroidogenically active
|
|
|
• granulosa cells exhibit increased proliferation
|
|
|
• after 3 months of age, ovaries contain increased numbers of corpora lutea
|
|
|
• females exhibit increased follicle growth
• numbers of apoptotic follicles decreased in eCG-primed mutant ovaries
|
|
|
• after 3 months of age, ovaries are larger and contain increased numbers of corpora lutea
|
|
|
• immature females primed with a superovulatory regiment of equine chorionic gonadotropin (eCG), followed by human CG, ovulate more oocytes than control mice, indicating advanced ovulation rate and increased ovulation
|
|
|
• luteolysis is dramatically impaired and delayed in mutants on a superovulatory regimen of eCG/hCG compared to wild-type mice
|
|
|
• females give birth to approximately 20% more pups than controls during a 6-month breeding period
|
|
|
• numbers of cleaved caspase 3 (CC3)-positive granulosa cells are decreased in eCG-primed mutant ovaries
|
|
|
• the increased numbers of corpora lutea are at different stages of differentiation than in controls
• steroid biosynthesis is similar in mutants as in controls indicating that even though life span of corpora lutea are extended, they do not remain steroidogenically active
|
|
|
• granulosa cells exhibit increased proliferation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination develop ovarian cancer eight weeks after injection
|
|
|
• mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination develop ovarian cancer eight weeks after injection
|
|
|
• mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination develop ovarian cancer eight weeks after injection
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:161953 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• triple mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination are protected from developing ovarian cancer, with only 1 of 11 mice developing cancer compared to 9 of 12 double Kras and Pten mutants
|
|
• triple mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination are protected from developing ovarian cancer, with only 1 of 11 mice developing cancer compared to 9 of 12 double Kras and Pten mutants
|
|
• triple mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination are protected from developing ovarian cancer, with only 1 of 11 mice developing cancer compared to 9 of 12 double Kras and Pten mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mammary glands exhibit much larger lobules on the 13th day of pregnancy
|
|
• develop mammary gland tumors as early as 2 months of age
• tumor incidence is increased with shortened latencies in multiparous females
|
|
• benign fibroadenomas
|
|
• pleiomorphic adenocarcinomas
|
|
|
• delay in the normal involution process and a decrease in cell apoptosis
|
|
|
• mammary glands exhibit much larger lobules on the 13th day of pregnancy
|
|
|
• virgin mammary duct epithelium exhibits increased proliferation at 5 weeks and 14 weeks of age
|
|
|
• virgin mammary ducts develop excessive side branches or small protrusions at 6 weeks of age
|
|
|
• mammary ducts grow much faster during puberty than in controls, leading to earlier occupancy of the fat pad and earlier disappearance of the terminal end buds than in controls
|
|
|
• virgin glands contain many lobuloalveolar buds which are normally seen during pregnancy indicating an acceleration in lobuloalveolar-like precocious differentiation
|
|
• develop mammary gland tumors as early as 2 months of age
• tumor incidence is increased with shortened latencies in multiparous females
|
|
• benign fibroadenomas
|
|
• pleiomorphic adenocarcinomas
|
|
|
• mammary glands after one pregnancy show intra-luminal focal cellular hyperplasia and dysplasia
|
|
|
• delay in the normal involution process and a decrease in cell apoptosis
|
|
|
• mammary glands exhibit much larger lobules on the 13th day of pregnancy
|
|
|
• virgin mammary duct epithelium exhibits increased proliferation at 5 weeks and 14 weeks of age
|
|
|
• virgin mammary ducts develop excessive side branches or small protrusions at 6 weeks of age
|
|
|
• mammary ducts grow much faster during puberty than in controls, leading to earlier occupancy of the fat pad and earlier disappearance of the terminal end buds than in controls
|
|
|
• virgin glands contain many lobuloalveolar buds which are normally seen during pregnancy indicating an acceleration in lobuloalveolar-like precocious differentiation
|
|
• develop mammary gland tumors as early as 2 months of age
• tumor incidence is increased with shortened latencies in multiparous females
|
|
• benign fibroadenomas
|
|
• pleiomorphic adenocarcinomas
|
|
|
• mammary glands after one pregnancy show intra-luminal focal cellular hyperplasia and dysplasia
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• brown adipose tissue shows hypertrophy, accompanied by presence of large unilocular adipocytes
|
| N |
• mice shown normal glucose metabolism, with reversal of hyperglycemia to a level that is lower than in wild-type mice and normalized response to glucose challenge
|
|
• mice develop malignant sarcomas by 3 months of age at various locations of the body, including diaphragm, limb, spine, retroperitoneum, subcutaneous regions, and in the thoracic cavity
• multiple tumors of various sizes are seen in all mice
• tumors show classical biphasic neoplasm with one component of atypical lipomatous tumors and a second component of high-grade sarcoma indicating dedifferentiated liposarcoma
• tumors show heavy infiltration of inflammatory cells which are Cd45+/Ki67-
• treatment with rosigliatazone starting from 3 weeks of age prevents liposarcoma formation at 5 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• prostatic ductules of mutants infected with an adenovirus expressing Cre recombinase exhibit a mixed phenotype containing mostly normal, organized epithelial cells and patches of large, disorganized hyperplastic cells; inefficient deletion of Rictor is seen in the patches of disorganized hyperplastic cells
|
|
|
• prostate tissue histology of mutants infected with an adenovirus expressing Cre recombinase appears normal except that epithelial cells are slightly smaller
|
|
|
• prostatic ductules of mutants infected with an adenovirus expressing Cre recombinase exhibit a mixed phenotype containing mostly normal, organized epithelial cells and patches of large, disorganized hyperplastic cells; inefficient deletion of Rictor is seen in the patches of disorganized hyperplastic cells
|
|
|
• prostate tissue histology of mutants infected with an adenovirus expressing Cre recombinase appears normal except that epithelial cells are slightly smaller
|
|
• mutants infected with an adenovirus expressing Cre recombinase do not develop prostate adenocarcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 60% incidence of granulosa cell tumor occurrence, with early tumor development
• granulosa cell tumors are either solid and surrounded by a thin layer of ovarian tissue containing a few growing follicles or are larger and contain tubular-like structures of different sizes and shapes surrounded by a basal lamina of collagen IV
• mice injected with superovulatory levels of equine gonadotropin and human gonadotropin at 6 weeks of age develop large granulosa cell tumors early
|
|
|
• tumor bearing mice exhibit increased levels of serum inhibin A and inhibin B
|
|
|
• serum follicle stimulating hormone levels are below the level of detection in tumor bearing mice
|
|
|
• serum luteinizing hormone levels are below the level of detection in tumor bearing mice
|
|
|
• 60% incidence of granulosa cell tumor occurrence, with early tumor development
• granulosa cell tumors are either solid and surrounded by a thin layer of ovarian tissue containing a few growing follicles or are larger and contain tubular-like structures of different sizes and shapes surrounded by a basal lamina of collagen IV
• mice injected with superovulatory levels of equine gonadotropin and human gonadotropin at 6 weeks of age develop large granulosa cell tumors early
|
|
|
• 60% incidence of granulosa cell tumor occurrence, with early tumor development
• granulosa cell tumors are either solid and surrounded by a thin layer of ovarian tissue containing a few growing follicles or are larger and contain tubular-like structures of different sizes and shapes surrounded by a basal lamina of collagen IV
• mice injected with superovulatory levels of equine gonadotropin and human gonadotropin at 6 weeks of age develop large granulosa cell tumors early
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• average beta cell size is increased by 31% compared to controls and by 15% compared to single conditional Pten mutants
• however, mutants show normal beta cell proliferation
|
|
• beta cell mass is about 40% lower than that of single conditional Pten mutants
|
|
• total glucose excursion is lower compared to single conditional Rictor mutants
|
|
• fed blood glucose concentration remains similar to the controls, however mutants show a lower blood glucose concentration at 30 and 60 min after an intraperitoneal glucose bolus compared to single conditional Rictor mutants
|
|
• mutants exhibit lower plasma insulin levels 15 min after glucose challenge and lower total insulin output compared with controls
• however, insulin secretion by glucose stimulated islets is similar to controls and pancreatic insulin content is unchanged
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion
|
|
|
• castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion
(J:153425)
• mutants show extensive prostate intraepithelial neoplasia (PIN) III and PIN IV 9-12 months after tamoxifen induction, with some areas of squamous papilloma, however mutants rarely develop lethal prostate cancer up to 2 years following tamoxifen induction
(J:191327)
|
|
|
• castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion
|
|
|
• castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion
(J:153425)
• mutants show extensive prostate intraepithelial neoplasia (PIN) III and PIN IV 9-12 months after tamoxifen induction, with some areas of squamous papilloma, however mutants rarely develop lethal prostate cancer up to 2 years following tamoxifen induction
(J:191327)
|
|
|
• castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion
|
|
|
• castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion
(J:153425)
• mutants show extensive prostate intraepithelial neoplasia (PIN) III and PIN IV 9-12 months after tamoxifen induction, with some areas of squamous papilloma, however mutants rarely develop lethal prostate cancer up to 2 years following tamoxifen induction
(J:191327)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice show reduced prostate growth, with a decrease prostate cancer progression and cell proliferation compared to Ptentm1Hwu/Ptentm1Hwu Tg(Pbsn-cre)4Prb/0 Tg(CAG-MYC,-GFP)#Rugg/0 mice
|
|
|
• mice show reduced prostate growth, with a decrease prostate cancer progression and cell proliferation compared to Ptentm1Hwu/Ptentm1Hwu Tg(Pbsn-cre)4Prb/0 Tg(CAG-MYC,-GFP)#Rugg/0 mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mutants die before 10 months of age
|
|
• increase in branching of bile ducts in the liver
|
|
• increase in branching of bile ducts in the liver
|
|
• increase in liver size and weight due to fat accumulation in the liver
|
|
• at 2 months of age, hyperplastic foci emerge from bile ducts and continue to grow, leading to tumor formation in all mice at 4-7 months of age; tumors are intrahepatic cholangiocellular carcinoma
|
|
• at 2 months of age, hyperplastic foci emerge from bile ducts and continue to grow, leading to tumor formation in all mice at 4-7 months of age; tumors are intrahepatic cholangiocellular carcinoma
|
|
• increase in liver size and weight due to fat accumulation in the liver
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• most females lack ovarian abnormalities
|
|
|
• 5 of 70 females developed ovarian tumors
(J:142150)
• ovarian tumors are granulosa cell tumors
(J:142150)
• 65% of mice develop granulosa-cell type tumors in the ovary
(J:222579)
• however, mice do not develop ovarian or fallopian tube high grade serous carcinoma
(J:222579)
|
|
|
• many females fail to carry pregnancies to term
|
|
• many females have small litters due to fetal death after E9.5
|
|
|
• 5 of 70 females developed ovarian tumors
(J:142150)
• ovarian tumors are granulosa cell tumors
(J:142150)
• 65% of mice develop granulosa-cell type tumors in the ovary
(J:222579)
• however, mice do not develop ovarian or fallopian tube high grade serous carcinoma
(J:222579)
|
|
• ganulosa cell tumors are aggressive and metastasize to the lungs
|
|
|
• 5 of 70 females developed ovarian tumors
(J:142150)
• ovarian tumors are granulosa cell tumors
(J:142150)
• 65% of mice develop granulosa-cell type tumors in the ovary
(J:222579)
• however, mice do not develop ovarian or fallopian tube high grade serous carcinoma
(J:222579)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 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
|
|
• females develop ovarian granulosa cell bilateral tumors with 100% penetrance from an early age
|
|
|
• 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
|
|
• 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)
|
|
|
• seminiferous tubule degeneration is seen by 3 weeks of age
|
|
|
• 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
|
|
• females develop ovarian granulosa cell bilateral tumors with 100% penetrance from an early age
|
|
|
• 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
|
|
|
• seminiferous tubule degeneration is seen by 3 weeks of age
|
|
|
• 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
|
|
• females develop ovarian granulosa cell bilateral tumors with 100% penetrance from an early age
|
|
|
• 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
|
|
• pulmonary tumor cell embolisms
|
|
• extrensive extramedullary hematopoiesis
|
|
• female mice die before 9 weeks of age
|
|
• pulmonary tumor cell embolisms
|
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 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• female mutants develop granulosa cell tumors by 3 weeks of age
|
|
|
• male mutants develop testicular granulosa cell tumors by 5 weeks of age
|
|
|
• female mutants develop granulosa cell tumors by 3 weeks of age
|
|
|
• male mutants develop testicular granulosa cell tumors by 5 weeks of age
|
|
|
• female mutants develop granulosa cell tumors by 3 weeks of age
|
|
|
• male mutants develop testicular granulosa cell tumors by 5 weeks of age
|
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 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• no abnormalities in testis
|
|
|
• mean mutant mesometrial maternal decidua surface area is 2.81-fold greater than in controls
• decidua are abnormal in appearance, featuring many mitotic figures in females 11.5 days pregnant, with little evidence of apoptosis, and many cells with unusually abundant cytoplasm, particularly near the trophoblast invasion front
• 9-fold decrease in apoptotic decidaul cells in mutants relative to controls
• about 2-3 days after expected parturition in the second gestation, females show necrotic decidua with transmural pyometritis and edema in the endometrial stroma
• these results indicate failure of decidual regression
|
|
|
• mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc
|
|
|
• endometrium epithelial cells appear hypertrophic, hyperplastic, and disorganized
• about 2-3 days after expected parturition of the second gestation, females show necrotic decidua with transmural pyometritis and edema in the endometrial stroma
|
|
|
• endometrial fibrosis is seen in females beyond the first gestation at day 112.5 and day 119.45 pc
|
|
|
• thickening of the myometrium and disorganization of the muscle fibers before and throughout gestation
|
|
|
• uteri of pregnant females beyond the first gestation, show varying degrees of hyperplasia of both the uterine and glandular epithelia
|
|
|
• primiparous females exhibit reduced fertility due to increased fetal loss at E11.5
• almost all mutant females fail to carry a second litter to term; females pregnant for the second time show signs of implantation but no viable fetuses at 9.5 dpc
|
|
• females produce about 44% fewer pups per mating than controls
• implanted fetuses fail to develop to term due to epithelial hyperplasia and other uterine anomalies
|
|
|
• females at 11.5 days of pregnancy exhibit poorly transformed maternal vasculature in the decidua, showing persistence of the muscular layer of maternal vessels, even deep within the decidual tissue, however maternal vascular transformation appears complete by 14.5 dpc, indicating a transient delay in vasculature transformation
|
|
|
• mean mutant mesometrial maternal decidua surface area is 2.81-fold greater than in controls
• decidua are abnormal in appearance, featuring many mitotic figures in females 11.5 days pregnant, with little evidence of apoptosis, and many cells with unusually abundant cytoplasm, particularly near the trophoblast invasion front
• 9-fold decrease in apoptotic decidaul cells in mutants relative to controls
• about 2-3 days after expected parturition in the second gestation, females show necrotic decidua with transmural pyometritis and edema in the endometrial stroma
• these results indicate failure of decidual regression
|
|
|
• mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc
|
|
|
• abnormal development of the placental labyrinth, and frequent apparent intrauterine fetal growth restriction
• by 11.5 dpc, the placental labyrinth is thin and underdeveloped in most concepti of mutant females
|
|
• by 11.5 dpc, trophoblast migration appears restricted by an abnormally thick maternal decidua
• fetal trophoblast glycogen cells do not migrate beyond the parietal trophoblast giant cell border by 14.5 dpc as in controls and are halted at the maternal-fetal interface
• trophoblast migration is impeded by inhibition of decidual regression and is attributable to inhibition of decidual cell apoptosis
|
|
|
• mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc
|
|
|
• mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc
|
|
|
• females at 11.5 days of pregnancy exhibit poorly transformed maternal vasculature in the decidua, showing persistence of the muscular layer of maternal vessels, even deep within the decidual tissue, however maternal vascular transformation appears complete by 14.5 dpc, indicating a transient delay in vasculature transformation
|
|
|
• mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mutants die within 2-3 months of age due to tumor burden
|
|
|
• mutants exhibit precancerous lesions in the ovaries by 3 weeks of age
|
|
|
• mutants develop large granulosa cell tumors by 6-8 weeks of age
|
|
|
• granulosa cell apoptosis is decreased in the ovaries at 5-6 weeks of age
|
|
|
• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked
|
|
|
• granulosa cell proliferation is increased in the ovaries at 5-6 weeks of age
|
|
|
• mutants exhibit precancerous lesions in the ovaries by 3 weeks of age
|
|
|
• mutants develop large granulosa cell tumors by 6-8 weeks of age
|
|
|
• granulosa cell apoptosis is decreased in the ovaries at 5-6 weeks of age
|
|
|
• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked
|
|
|
• granulosa cell proliferation is increased in the ovaries at 5-6 weeks of age
|
|
|
• mutants exhibit precancerous lesions in the ovaries by 3 weeks of age
|
|
|
• mutants develop large granulosa cell tumors by 6-8 weeks of age
|
|
• by 6 weeks of age
|
|
• by 6 weeks of age
|
|
• by 6 weeks of age
|
|
• by 6 weeks of age
|
|
|
• granulosa cell apoptosis is decreased in the ovaries at 5-6 weeks of age
|
|
|
• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked
|
|
|
• granulosa cell proliferation is increased in the ovaries at 5-6 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 |
|
• 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 |
|
• enlarged follicles
|
|
• mutants have an enlarged thyroid at 2 years of age and exhibit a goiter-like phenotype, but do not show development of tumors
|
|
• P14 mutants show an increase in T4 levels
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants exhibit accelerated development of acinar-to-ductal metaplasia, malignant pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma compared to single heterozygous Kras mutants, with almost 100% of mutants succumbing to cancer by 12 months of age
• 21 of 25 mice alive past 2 months of age develop well-to-moderately differentiated invasive ductal cancers
• rare metastasis to lungs is seen
|
|
• at 3 months of age, 8 of 12 mutants show development of pancreatic ductal adenocarcinoma (PDAC), and all mice show PDAC by 6 months of age
• loss of Pten heterozygosity is seen during pancreatic ductal adenocarcinoma progression but not in mPanIN lesions
|
|
• mutants show malignant pancreatic intraepithelial neoplasia (mPanIN) development starting at 1 month of age, and all show mPanIN by 3 months of age
|
|
• median survival time is about 3.5 months
|
|
• acinar-to-ductal metaplasia is seen at 1-3 months of age, concentrated in the transition zone between morphologically normal pancreatic structures and mPanIN and PDAC lesions
• acinar-to-ductal metaplasia development precedes mPanIN formation
• metaplastic lesions show an increase in CD44+ cells
|
|
• mutants exhibit accelerated development of acinar-to-ductal metaplasia, malignant pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma compared to single heterozygous Kras mutants, with almost 100% of mutants succumbing to cancer by 12 months of age
• 21 of 25 mice alive past 2 months of age develop well-to-moderately differentiated invasive ductal cancers
• rare metastasis to lungs is seen
|
|
• at 3 months of age, 8 of 12 mutants show development of pancreatic ductal adenocarcinoma (PDAC), and all mice show PDAC by 6 months of age
• loss of Pten heterozygosity is seen during pancreatic ductal adenocarcinoma progression but not in mPanIN lesions
|
|
• mutants show malignant pancreatic intraepithelial neoplasia (mPanIN) development starting at 1 month of age, and all show mPanIN by 3 months of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:164210 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• Background Sensitivity: unlike on the congenic C57BL/6 background, mutants on the BALB/c background have normal T4 and TSH levels
|
|
• after naphthalene administration to induce lung injury, the proximal airway epithelium at 3 and 7 days post injury appears intact with no signs of injury
• after naphthalene administration to induce lung injury, the level of injury in the bronchial airway epithelium is reduced and repair is enhanced compared to controls
|
|
• mutants exhibit an increase in the proliferation rate of the epithelial cells in E15.5 lungs
• expansion of epithelial cell populations occurs in multiple progenitor cell niches of the lungs including the tracheal basal cells in the proximal lung, the neuroepithelial bodies (NEB) in the distal bronchi and the progenitor cells occupying the bronchioalveolarduct junction (BADJ) region
|
|
• lungs exhibit increased cell proliferation and decreased apoptosis
• lungs at 8 weeks of age sometimes contain a mass consisting of epithelial cells (putative progenitor cell masses) around the BADJ area; masses are slow growing and are organized into ductlike structures
|
|
• progressive epithelial hyperplasia extending from the trachea to the small bronchioles is seen in the proximal lung epithelium from early stages of lung development and in adults
|
|
• marker analysis indicates a block in transition from precursor to terminally differentiated cell types indicating impaired epithelial cell fate determination in the lung
|
|
• increase in number of Clara cells in the lungs and a decrease in the number of ciliated cells, the terminally differentiated progeny of Clara cells
|
|
• mutants exhibit an increase in the proliferation rate of the epithelial cells in E15.5 lungs
• expansion of epithelial cell populations occurs in multiple progenitor cell niches of the lungs including the tracheal basal cells in the proximal lung, the neuroepithelial bodies (NEB) in the distal bronchi and the progenitor cells occupying the bronchioalveolarduct junction (BADJ) region
|
|
• Background Sensitivity: at P14, epithelial cell proliferation rates in the thyroid are lower on the mixed BALB/c background than on the congenic C57BL/6 background
• at P14, thyroid architecture is conserved but an increase in the number of epithelial cells along the follicles is seen, resembling a goiter disease
|
| N |
• Background Sensitivity: mutants survive to adulthood on the BALB/c background without presenting any obvious pathological conditions unlike mice on the congenic C57BL/6 background
|
|
• progressive epithelial hyperplasia extending from the trachea to the small bronchioles is seen in the proximal lung epithelium from early stages of lung development and in adults
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mutants develop pancreatic ductal adenocarcinoma by 3 weeks of age
|
|
• mutants show severe exocrine pancreatic atrophy and edema along with the presence of mPanINs, metaplasias, and ducto-insular complexes and pancreatic ductal adenocarcinoma at P17
|
|
• severe
|
|
• mutants exhibit acinar-to-ductal metaplasia
|
|
• all mutants develop pancreatic ductal adenocarcinoma by 3 weeks of age
|
|
• mutants are moribound by weaning, with a median survival of about 17 days
|
|
• mutants show severe exocrine pancreatic atrophy and edema along with the presence of mPanINs, metaplasias, and ducto-insular complexes and pancreatic ductal adenocarcinoma at P17
|
|
• severe
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:164210 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• beta-cell size is increased by 15% compared to controls
• number of proliferating beta-cells is increased by 34% compared to controls
|
|
• beta-cell mass is 86% higher than controls after adjusting for body size
• however, pancreatic insulin content is unchanged and insulin sensitivity is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 3 of 14 mice die by age 12 to 29 weeks
• however, all castrated mice survive from 7 to 10 months
|
|
• 12 month survival rate of mutants is 60% on the high-omega-3 diet, 10% on the low-omega-3 diet and 0% on the high-omega-6 diet
• mutants on a high-omega-6 diet do not survive beyond 10 months of age and die due to bladder obstruction by the prostate tumor compressing the urethra
|
|
|
• prostate lobes are enlarged and exhibit increased vascularity and cellularity
|
|
|
• at 4 weeks, epithelium cells in the lateral prostate are larger than in Ptentm1Hwu homozygotes
|
|
|
• without cellular atypia by 4 weeks of age
|
|
|
• mice exhibit progressive enlargement of the prostate gland compared to in Ptentm1Hwu homozygotes
• however, castration reduces prostate size
|
|
|
• prostate weight is higher than in controls starting at 8 weeks of age
• prostate weight gain from 5 to 24 weeks is significantly less in mice fed a high-omega-3 diet than in mice fed a high-omega-6 diet
|
|
|
• at 4 weeks, mice develop multifocal hyperplasia compared to in Ptentm1Hwu homozygotes
• hyperplasia is initially observed in the dorsolateral and ventral lobe with subsequent involvement of the anterior lobes
|
|
|
• males develop prostate cancer
|
|
|
• mice develop invasive adenocarcinoma by 9 weeks of age in all lobes
(J:93902)
• prostate cancers are metastatic
(J:93902)
• castrated mice still develop invasive adenocarcinoma
(J:93902)
• 80% of mutants fed a high-omega-6 diet develop invasive carcinoma while 50% of mutants fed a high-omega-3 diet develop invasive carcinoma
(J:124208)
|
|
|
• by 6 weeks of age, all mice develop prostate intraepithelial neoplasia
(J:93902)
• latency to prostate intraepithelial neoplasia is 1.5 months
(J:93902)
• males develop PIN lesions after 16 months of age
(J:106650)
|
|
|
• prostate cancer cells exhibit increased proliferation compared to in Ptentm1Hwu homozygotes
(J:93902)
• cancer cells induce a desmoplastic response
(J:93902)
• castrated mice exhibit increased proliferation compared with similarly treated Ptentm1Hwu homozygotes
(J:93902)
• higher numbers of apoptotic cells are seen in mutant prostates from mice on the high-omega-3 diet than on the high-omega-6 diet
(J:124208)
|
|
|
• cancer cells induce inflammation
|
|
|
• males develop prostate cancer
|
|
|
• mice develop invasive adenocarcinoma by 9 weeks of age in all lobes
(J:93902)
• prostate cancers are metastatic
(J:93902)
• castrated mice still develop invasive adenocarcinoma
(J:93902)
• 80% of mutants fed a high-omega-6 diet develop invasive carcinoma while 50% of mutants fed a high-omega-3 diet develop invasive carcinoma
(J:124208)
|
|
|
• by 6 weeks of age, all mice develop prostate intraepithelial neoplasia
(J:93902)
• latency to prostate intraepithelial neoplasia is 1.5 months
(J:93902)
• males develop PIN lesions after 16 months of age
(J:106650)
|
|
• omega-3 polyunsaturated fatty acids (PUFAs) slow the progression of prostate tumors in 5- to 8-week old mutants; once carcinoma develops, omega-3 PUFAs induce apoptosis and decrease the growth of the tumor
|
|
|
• cancer cells induce inflammation
|
|
• mutants surviving 6 months or longer exhibit pyelonephritis
|
|
|
• prostate lobes are enlarged and exhibit increased vascularity and cellularity
|
|
|
• at 4 weeks, epithelium cells in the lateral prostate are larger than in Ptentm1Hwu homozygotes
|
|
|
• without cellular atypia by 4 weeks of age
|
|
|
• mice exhibit progressive enlargement of the prostate gland compared to in Ptentm1Hwu homozygotes
• however, castration reduces prostate size
|
|
|
• prostate weight is higher than in controls starting at 8 weeks of age
• prostate weight gain from 5 to 24 weeks is significantly less in mice fed a high-omega-3 diet than in mice fed a high-omega-6 diet
|
|
|
• at 4 weeks, mice develop multifocal hyperplasia compared to in Ptentm1Hwu homozygotes
• hyperplasia is initially observed in the dorsolateral and ventral lobe with subsequent involvement of the anterior lobes
|
|
|
• males develop prostate cancer
|
|
|
• mice develop invasive adenocarcinoma by 9 weeks of age in all lobes
(J:93902)
• prostate cancers are metastatic
(J:93902)
• castrated mice still develop invasive adenocarcinoma
(J:93902)
• 80% of mutants fed a high-omega-6 diet develop invasive carcinoma while 50% of mutants fed a high-omega-3 diet develop invasive carcinoma
(J:124208)
|
|
|
• by 6 weeks of age, all mice develop prostate intraepithelial neoplasia
(J:93902)
• latency to prostate intraepithelial neoplasia is 1.5 months
(J:93902)
• males develop PIN lesions after 16 months of age
(J:106650)
|
|
|
• prostate cancer cells exhibit increased proliferation compared to in Ptentm1Hwu homozygotes
(J:93902)
• cancer cells induce a desmoplastic response
(J:93902)
• castrated mice exhibit increased proliferation compared with similarly treated Ptentm1Hwu homozygotes
(J:93902)
• higher numbers of apoptotic cells are seen in mutant prostates from mice on the high-omega-3 diet than on the high-omega-6 diet
(J:124208)
|
|
|
• cancer cells induce inflammation
|
|
• mutants surviving 6 months or longer exhibit retention of urine in the anterior prostate lobes
|
|
• mutants surviving 6 months or longer exhibit pyelonephritis
|
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:93902 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• latency to prostate intraepithelial neoplasia is 8 to 10 months
|
|
|
• latency to prostate intraepithelial neoplasia is 8 to 10 months
|
|
|
• latency to prostate intraepithelial neoplasia is 8 to 10 months
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice fed a high-omega-6 diet exhibit significantly lower prostate weights than mice without Tg(CAG-fat-1)1Jxk
|
|
• mice fed a high-omega-6 diet exhibit a much lower omega-6/omega-3 ratio in the blood and prostate than mice without the Tg(CAG-fat-1)1Jxk transgene, indicating that fat-1 is able to convert most of the omega-6 polyunsaturated fatty acids to omega-3
|
|
|
• mice fed a high-omega-6 diet exhibit significantly lower prostate weights than mice without Tg(CAG-fat-1)1Jxk
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• enlarged prostate gland due to epithelial hyperplasia
|
|
|
• prostatic adenocarcinomas are seen from 9 months onward
• adenocarcinomas are seen in all lobes, although more often in the dorsolateral and ventral lobes than anterior lobes
• 6 of 17 mutants at 9-16.2 months of age and 9 of 10 mutants at 18.2-19.1 months exhibit adenocarcinomas
• adenocarcinomas show loss of heterozygosity of Pten
• 2 of 31 mutants develop a rare form of mucinous adenocarcinoma
|
|
|
• males by 6.5 months of age exhibit hyperplasia and focal-low grade PIN lesions in the prostate
• males older than 7.5 months of age exhibit high-grade PINs
|
|
|
• enlarged prostate gland due to epithelial hyperplasia
|
|
|
• prostatic adenocarcinomas are seen from 9 months onward
• adenocarcinomas are seen in all lobes, although more often in the dorsolateral and ventral lobes than anterior lobes
• 6 of 17 mutants at 9-16.2 months of age and 9 of 10 mutants at 18.2-19.1 months exhibit adenocarcinomas
• adenocarcinomas show loss of heterozygosity of Pten
• 2 of 31 mutants develop a rare form of mucinous adenocarcinoma
|
|
|
• males by 6.5 months of age exhibit hyperplasia and focal-low grade PIN lesions in the prostate
• males older than 7.5 months of age exhibit high-grade PINs
|
|
|
• prostatic adenocarcinomas are seen from 9 months onward
• adenocarcinomas are seen in all lobes, although more often in the dorsolateral and ventral lobes than anterior lobes
• 6 of 17 mutants at 9-16.2 months of age and 9 of 10 mutants at 18.2-19.1 months exhibit adenocarcinomas
• adenocarcinomas show loss of heterozygosity of Pten
• 2 of 31 mutants develop a rare form of mucinous adenocarcinoma
|
|
|
• males by 6.5 months of age exhibit hyperplasia and focal-low grade PIN lesions in the prostate
• males older than 7.5 months of age exhibit high-grade PINs
|
|
• metastasis of adenocarcionma into lymph nodes is observed, with 50-60% penetrance
|
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:106650 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 70% of mutants exhibit enlarged thymus
|
|
• splenomegaly
|
|
• progressive development of myeloproliferative disorder and leukemogenesis in the chronic phase followed by blast crisis
|
|
• 2-3 months after birth, mutants show increased circulating neutrophils and white blood cells and leukemic blast invasion into hematopoietic and non-hematopoietic organs
|
|
• one month after birth, mutants develop a myeloid shift with increased neutrophil counts
|
|
• 70% of mutants exhibit enlarged thymus
|
|
• splenomegaly
|
|
• 2-3 months after birth, mutants show increased circulating neutrophils and white blood cells and leukemic blast invasion into hematopoietic and non-hematopoietic organs
|
|
• one month after birth, mutants develop a myeloid shift with increased neutrophil counts
|
|
• 70% of mutants exhibit enlarged lymph nodes
|
|
• hepatomegaly
|
|
• 74% of mutants develop T-lymphoblastic leukemia
|
|
• 26% of mutants develop acute myeloid leukemia
|
|
• 70% of mutants exhibit enlarged thymus
|
|
• hepatomegaly
|
|
• splenomegaly
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increase in brain size due to expansion of allocortex and neocortex
|
|
• apical dendrites of pyramidal neurons in cortical layer 2/3 but not layer 5 are longer and more tortuous than in controls
• total arbor length is on average 1.6 mm longer in mutants, indicating an approximate 80% expansion of the apical dendritic tree
• however, basal dendritic length is not different
• rapamycin treatments completely prevent dendritic growth seen following Pten deletion
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cysts exhibit a 3- to 6-fold increase in the number of Ki-67-positive kidney epithelial cells per mm2 of cortex
|
|
• mutants develop multiple epithelial tubule cysts in the kidney cortex and medulla
• cysts develop in all mice (14 of 14) and are seen as early as 6-8 weeks of age
• cysts arise in collecting ducts and distal tubules
• most cysts are lined by a single layer of epithelial cells (simple cysts), whereas ~8% of cysts are lined by multilayered epithelial cells with
occasional papillary projections (atypical cysts)
• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type
|
|
• mutants develop multiple epithelial tubule cysts in the kidney cortex
|
|
• mutants develop multiple epithelial tubule cysts in the kidney medulla
|
|
• males and females exhibit enlarged and heavier kidneys due to epithelial tubule cysts
|
|
• 3 of 14 mice show isolated regions of benign squamous metaplasia within the kidney cortex
|
|
• kidney epithelial cells fail to maintain their primary cilia, resulting in uncontrolled proliferation and cyst formation
|
|
• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type
|
|
• hyperproliferation of the urothelium in the renal pelvis is more pronounced than in single Pten mutants
|
|
• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type
|
|
• cysts exhibit a 3- to 6-fold increase in the number of Ki-67-positive kidney epithelial cells per mm2 of cortex
|
| N |
• no tumors areas seen at 3-6 months of age, when mice are euthanized to avoid renal failure
|
|
• mutants develop multiple epithelial tubule cysts in the kidney cortex and medulla
• cysts develop in all mice (14 of 14) and are seen as early as 6-8 weeks of age
• cysts arise in collecting ducts and distal tubules
• most cysts are lined by a single layer of epithelial cells (simple cysts), whereas ~8% of cysts are lined by multilayered epithelial cells with
occasional papillary projections (atypical cysts)
• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type
|
|
• mutants develop multiple epithelial tubule cysts in the kidney cortex
|
|
• mutants develop multiple epithelial tubule cysts in the kidney medulla
|
|
• males and females exhibit enlarged and heavier kidneys due to epithelial tubule cysts
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| von Hippel-Lindau disease | DOID:14175 |
OMIM:193300 |
J:137073 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mutants do not develop hydronephrosis
|
|
• hyperproliferation and enlarged epithelial cells in the ureter
|
|
• hyperproliferation and enlarged epithelial cells in the bladder
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mutants die within 80 days
|
|
• adenomas in the small intestine
|
|
• mutants develop an average of 20.1 intestinal polyps per mouse, an 11.17-fold increase over the numbers seen in heterozygous Apc mice
|
|
• adenomas in the small intestine
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increase in crypt cell proliferation
|
|
• intestine is 1.28-fold longer and weighs 1.58-fold more than controls
• however, mutants do not develop polyps
|
|
• thickening of the intestinal mucosa
|
|
• increase in the number and size of goblet cells
|
|
• decrease in the number of enteroendocrine cells
|
|
• thickening of the muscular layers of the small intestine
|
|
• small intestine exhibits an expanded crypt compartment with increased number of crypts per villus
|
|
• marker analysis indicates impaired Paneth cell maturation
|
|
• total protein content of the duodenum is enhanced by 50%
|
|
• jejunum exhibits expanded crypt and villus compartments, an increased number of crypts, thickening of the muscular layers and villus branching
|
|
• small intestine exhibits an expanded villus compartment
|
|
• mutants exhibit branching of the villi in the small intestine
|
|
• small intestine exhibits an expanded crypt compartment with increased number of crypts per villus
|
|
• marker analysis indicates impaired Paneth cell maturation
|
|
• increase in the number and size of goblet cells
|
|
• increase in crypt cell proliferation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival is on average 22 weeks
|
|
• mutants develop multiple visible subcutaneous tumors with 100% penetrance, starting from 4 months of age
• majority of tumors are located on the back and sides
|
|
• each mutant has more than one lesion with features of human neurofibroma and malignant peripheral nerve sheath tumor
|
|
• progressive development of malignant peripheral nerve sheath tumors (MPNST) from neurofibroma, with 100% of mutants showing MPNST when followed for 7 months
• Pten loss of heterozygosity in mutants correlates with MPNST transformation from neurofibromas
|
|
• each mutant has more than one lesion with features of human neurofibroma and malignant peripheral nerve sheath tumor
|
|
• progressive development of malignant peripheral nerve sheath tumors (MPNST) from neurofibroma, with 100% of mutants showing MPNST when followed for 7 months
• Pten loss of heterozygosity in mutants correlates with MPNST transformation from neurofibromas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| malignant peripheral nerve sheath tumor | DOID:5940 | J:154673 | ||
| neurofibromatosis 1 | DOID:0111253 |
OMIM:162200 |
J:154673 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cultured adult neural stem cells maintain their ability to differentiate into neurons for a longer time compared to wild-type cells
|
|
• in culture, neurospheres formed by adult neural stem cells are generally larger and the stem cells' capacity for self renewal is prolonged compared to wild-type cells
|
|
• 7 days after induction of limited stroke in the sensorimotor cortex, mice have more neuroblasts in the peri-infarct cortex compared to controls
• however, there is no difference in the number of new cells present at 90 days after stroke induction
|
|
• continuous increase in the weight and size of the olfactory bulb compared to controls starting at 2.5 months of age
• the granule cell layer volume is increased 2 fold at 3.5 months of age
• the increase in volume is due to an increase in the number of cells migrating from the subependymal zone to the olfactory bulb and a decrease in the number of apoptotic cells in the granule cell layer
|
|
• increase in the volume of the subependymal zone compared to controls
• increase in the number of proliferating cells and DCX positive neuroblasts
|
|
• expansion of the adult neural stem cell and progenitor populations in the subependymal zone
|
|
• habituate faster to a novel odorant compared to controls
• however, no difference in response is seen on the first exposure to a novel odorant
|
|
• mice recover olfactory ability more quickly following exposure to dichlobenil compared to controls
|
| N |
• in contrast to other conditional null Pten genotypes no tumors are found in mice up to 2 years of age
(J:146630)
(J:154673)
|
|
• 7 days after induction of limited stroke in the sensorimotor cortex, mice have more neuroblasts in the peri-infarct cortex compared to controls
• however, there is no difference in the number of new cells present at 90 days after stroke induction
|
|
• cultured adult neural stem cells maintain their ability to differentiate into neurons for a longer time compared to wild-type cells
|
|
• in culture, neurospheres formed by adult neural stem cells are generally larger and the stem cells' capacity for self renewal is prolonged compared to wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• females exhibit prematurely activated primordial follicles (transient follicles with enlarged oocytes surrounded by flattened pre-granulosa cells) leading to complete depletion of follicles by 16 weeks of age
|
|
|
• females exhibit prematurely activated primordial follicles (transient follicles with enlarged oocytes surrounded by flattened pre-granulosa cells) leading to complete depletion of follicles by 16 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice survive 57 days unlike control mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• tamoxifen-treated mice develop T cell acute lymphoblastic leukemia unlike control mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• scruffy coat in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice survive 65 days compared with Pdk1tm1Dral Gt(ROSA)26Sortm9(cre/ESR1)Arte mice that survive 57
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• numbers of bronchioalveolar stem cells in terminal bronchi are normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• bronchioles exhibit clusters of CCSP+SPC+ cells (indicators of BASCs) as early as 4 weeks of age that are not seen in controls
|
|
• mutants exhibit expansion of bronchioalveolar stem cells (BASCs) in terminal bronchi
• small bronchi exhibit clusters of CCSP+SPC+ cells (indicators of BASCs) as early as 4 weeks of age that are not seen in controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increase in the numbers of Clara cells in the lungs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Altered dopamine neurons in the ventral midbrain of Ptentm1Hwu/Ptentm1Hwu Slc6a3tm1.1(cre)Bkmn/Slc6a3+ mice
| N |
• no difference in locomotor activity is seen compared to controls during exposure to a novel environment
|
|
• mutants exhibit a significant reduction in ipsilateral rotational behavior in response to amphetamine administration after 6OHDA lesioning
|
|
• neuronal hypertrophy in the ventral midbrain resulting in enlargement of the ventral midbrain area
• increase in the number of TH positive neurons in the substantia nigra compacta and ventral tegmental area of the adult ventral midbrain and an increase in neuronal soma size
|
|
• increase in the number of TH positive neurons in the substantia nigra compacta
|
|
• increase in the number of dopaminergic neuron dendritic processes in the substantia nigra pars reticulata
|
|
• modest but significant enlargement of the caudal striatum
|
|
• increase in number of dopaminergic neurons and fibers in the ventral mesencephalon
• dopaminergic neurons in the ventral midbrain are larger in size and have an increase in the number of dendritic processes in the substantia nigra pars reticulata
|
|
• hypertrophy of dopamine neurons
|
|
• mutant dopamine neurons are protected from 6OHDA induced lesions, fiber loss, and axonal loss in the striatum compared to controls
|
|
• increase in total dopamine tissue levels in the dorsal striatum and midbrain, however, no alterations in basal dopamine extracellular levels or evoked dopamine release in the dorsal striatum
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• thymus weight is similar to controls at 6-8 weeks of age unlike in mutant mice wild-type for Pkn3
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 6-8 weeks of age
|
|
• at 6-8 weeks of age
|
|
• at 6-8 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants injected with poly(I:C) to induce cre expression, exhibit 25% more platelets in the blood than controls
|
|
• collagen-induced platelet activation is enhanced in mutants injected with poly(I:C) to induce cre expression
|
|
• platelets of mutants injected with poly(I:C) to induce cre expression are induced to aggregate by a much lower level of collagen than is required to induce the same response by wild-type platelets
|
|
• collagen-induced platelet activation is enhanced in mutants injected with poly(I:C) to induce cre expression
|
|
• platelets of mutants injected with poly(I:C) to induce cre expression are induced to aggregate by a much lower level of collagen than is required to induce the same response by wild-type platelets
|
|
• mutants injected with poly(I:C) to induce cre expression have an average bleeding time that is shorter than in controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice show decreased overall survival, with a mean life span of 75 weeks
|
|
|
• mice develop prostatic adenocarcinoma by 10 weeks of age
• mice with developed tumors treated with a small-molecule inhibitor of P-eIF2alpha activity, ISRIB, show tumor regression within 3 weeks of treatment, with no signs of toxicity
|
|
|
• mice show enlargement of prostate growth by 6 weeks of age and accelerated development of high-grade prostatic intraepithelial neoplasia compared to single conditional Ptentm1Hwu mutants
|
|
|
• mice develop prostatic adenocarcinoma by 10 weeks of age
• mice with developed tumors treated with a small-molecule inhibitor of P-eIF2alpha activity, ISRIB, show tumor regression within 3 weeks of treatment, with no signs of toxicity
|
|
|
• mice show enlargement of prostate growth by 6 weeks of age and accelerated development of high-grade prostatic intraepithelial neoplasia compared to single conditional Ptentm1Hwu mutants
|
|
|
• mice develop prostatic adenocarcinoma by 10 weeks of age
• mice with developed tumors treated with a small-molecule inhibitor of P-eIF2alpha activity, ISRIB, show tumor regression within 3 weeks of treatment, with no signs of toxicity
|
|
|
• mice show enlargement of prostate growth by 6 weeks of age and accelerated development of high-grade prostatic intraepithelial neoplasia compared to single conditional Ptentm1Hwu mutants
|
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:261540 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mutants are protected from developing diabetes, and despite severe insulin resistance, mutants remain euglycemic and show normal glucose tolerance
|
|
• mutant islets show increased beta-cell function, showing robust insulin secretion after glucose stimulation compared to diminished insulin secretion in single homozygous Leprdb mice
|
|
• mutants exhibit a similar degree of insulin resistance as single Leprdb mice
|
|
• mutants exhibit a similar degree of weight gain as single homozygous Leprdb mice
|
|
• islets show similar degrees of hypertrophy and proliferation as those in single homozygous Leprdb mice and do not show a further increase in beta-cell mass compared to the single Leprdb mice
|
|
• mutant islets show increased beta-cell function, showing robust insulin secretion after glucose stimulation compared to diminished insulin secretion in single homozygous Leprdb mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice injected with tamoxifen at 2-3 weeks of age, exhibit islet hyperplasia but no ductal abnormalities or increase in DBA staining
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop hyperplastic lesions in the bladder unlike wild-type mice that are larger than in Apctm1Tno/Apctm1Tno Tg(Cyp1a1-cre/ERT)1Dwi mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at about 2-3 months of age, mutants show signs of illness, with wasting, respiratory distress and frequently die before 6 months of age
|
|
• mice exhibit ductal metaplasia that appears to result from expansion of centroacinar cells rather than transdifferentiation of acinar cells
|
|
• mutants exhibit progressive replacement of the acinar pancreas with highly proliferative ductual structures that contain abundant mucins and markers of pancreatic progenitor cells
• preweaned mutants show a 4-fold increase in BrdU incorporation in the acinar pancreas, particularly in the centroacinar position and epithelial cells within large ducts, indicating increased proliferation
|
|
• increase in centroacinar cells in the pancreas that are present in groups of 4-8 cells compared to single or doublet centroacinar cells in wild-type
|
|
• increase in centroacinar cell proliferation and an increase in apoptosis of acinar cells in transitional areas
|
|
• mice exhibit ductal metaplasia that appears to result from expansion of centroacinar cells rather than transdifferentiation of acinar cells
|
|
• mutants exhibit progressive replacement of the acinar pancreas with highly proliferative ductual structures that contain abundant mucins and markers of pancreatic progenitor cells
• preweaned mutants show a 4-fold increase in BrdU incorporation in the acinar pancreas, particularly in the centroacinar position and epithelial cells within large ducts, indicating increased proliferation
|
|
• increase in centroacinar cells in the pancreas that are present in groups of 4-8 cells compared to single or doublet centroacinar cells in wild-type
|
|
• increase in centroacinar cell proliferation and an increase in apoptosis of acinar cells in transitional areas
|
|
• newborns exhibit enlarged and irregularly shaped islets
|
|
• one 11-week old mutant developed papillary ductal adenocarcinoma while a 13-month old mutant developed a pancreatic ductal adenocarcinoma that invaded into the duodenum and exhibited a desmosplastic stroma
|
|
• mice exhibit widespread ductal metaplasia with increased mucin production and develop PanIN lesions and malignant transformation with low frequency
|
| N |
• fed and fasting blood glucose levels and glucose tolerance are normal
|
|
• mice exhibit widespread ductal metaplasia with increased mucin production and develop PanIN lesions and malignant transformation with low frequency
|
|
• 2 of 14 mice develop ductal malignancy in the pancreas
|
|
• one 11-week old mutant developed papillary ductal adenocarcinoma while a 13-month old mutant developed a pancreatic ductal adenocarcinoma that invaded into the duodenum and exhibited a desmosplastic stroma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop multiple polyps in the small intestine one month after completion of pIpC injection to induce Cre expression
• polyps show a large excess of crypt-like units at their base and aberrant positioning of crypts along the edges of villi
• overgrowth and insertions of stromal cells from the base of the polypoid mass are seen in the small intestine one month after completion of pIpC injection to induce Cre expression
• intestinal stem cells exhibit increased proliferation due to Akt activation and nuclear localization of beta-catenin resulting in an increase of intestinal stem cells in the crypts
• these excess stem cells initiate de novo crypt formation and crypt fission at a higher rate than in controls
|
|
• mice injected with pIpC to induce Pten deletion, develop myeloproliferative disease and T-cell acute lymphoblastic leukemia
|
|
• mice injected with pIpC to induce Pten deletion have an enlarged thymus
|
|
• mice injected with pIpC to induce Pten deletion have an enlarged spleen
|
|
• mean survival time of mice injected with pIpC to induce Pten deletion is 35 days
|
|
• mice injected with pIpC to induce Pten deletion have an enlarged thymus
|
|
• mice injected with pIpC to induce Pten deletion have an enlarged spleen
|
|
• mice injected with pIpC to induce Pten deletion have an enlarged thymus
|
|
• mice injected with pIpC to induce Pten deletion have an enlarged spleen
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| acute lymphoblastic leukemia | DOID:9952 |
OMIM:247640 OMIM:613065 |
J:169097 | |
| Cowden syndrome | DOID:6457 |
OMIM:PS158350 |
J:118329 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lifespan after pIpC treatment is shorter than in controls but longer than in mutant nice with one wild-type Pkn3 allele
|
|
• develop myeloproliferative neoplasms in the spleen 2 weeks after pIpC treatment
|
|
• all eventually develop T cell acute lymphoblastic leukemia after pIpC treatment at 6 weeks of age
|
|
• at 2 weeks after pIpC treatment
• thymus is smaller than in mutant mice with one wild-type Pkn3 allele
|
|
• at 2 weeks after pIpC treatment
|
|
• increase in the number of hematopoietic stem cells in the spleen 2 weeks after pIpC treatment
|
|
• at 2 weeks after pIpC treatment
• thymus is smaller than in mutant mice with one wild-type Pkn3 allele
|
|
• at 2 weeks after pIpC treatment
• thymus is smaller than in mutant mice with one wild-type Pkn3 allele
|
|
• at 2 weeks after pIpC treatment
|
|
• at 2 weeks after pIpC treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lifespan after pIpC treatment is shorter than in controls and in mutant nice with no wild-type Pkn3 alleles
|
|
• develop myeloproliferative neoplasms in the spleen 2 weeks after pIpC treatment
|
|
• all eventually develop T cell acute lymphoblastic leukemia after pIpC treatment at 6 weeks of age
|
|
• at 2 weeks after pIpC treatment
|
|
• at 2 weeks after pIpC treatment
|
|
• increase in the number of hematopoietic stem cells in the spleen 2 weeks after pIpC treatment
|
|
• at 2 weeks after pIpC treatment
|
|
• at 2 weeks after pIpC treatment
|
|
• at 2 weeks after pIpC treatment
|
|
• at 2 weeks after pIpC treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• islets are protected from oxidative stress
|
|
• increase in beta-cell proliferation at E17.5
|
|
• increase in beta cell size
• beta-cells maintain intact response to DNA-damaging stimuli unlike controls
|
|
• increase in beta cell mass, due to an increase in proliferation and in beta cell size
• however, mutants do not exhibit any further increase in beta-cell mass on a high-fat diet
|
|
• number of insulin-producing cells is increased in islets
|
|
• 1.5-fold increase in islet numbers
|
|
• 2-fold increase in islet size
|
|
• decrease in apoptotic rate during pancreas remodeling at P17
• however, pancreas exhibits normal islet functions
|
|
• increase in beta-cell proliferation at E17.5
|
|
• after high-fat diet feeding, mutants maintain robust insulin secretion in response to glucose compared to controls which show attenuation of insulin secretion, indicating that mutant islets are protected against high-fat diet-induced beta-cell dysfunction
|
| N |
• despite weight gain, mutants are protected from high-fat diet-induced diabetes, remaining euglycemic and showing improved glucose tolerance than controls on a high-fat diet
|
|
• after high-fat diet feeding, mutants maintain robust insulin secretion in response to glucose compared to controls which show attenuation of insulin secretion, indicating that mutant islets are protected against high-fat diet-induced beta-cell dysfunction
|
|
• hypoglycemia, however mice respond normally to a glucose challenge
|
|
• mutants are protected from high-fat diet-induced diabetes, remaining euglycemic and showing improved glucose tolerance than controls on a high-fat diet
|
|
• increase in peripheral insulin sensitivity
|
|
• mice are protected from STZ-induced beta-cell injury and diabetes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• progressive hepatocyte cell death as mice progress from steatosis to premalignancy, with massive hepatocyte death by 9 months of age
|
|
|
• at 12 months of age, livers show increased cell proliferation
|
|
|
• progressive and chronic liver injury that begins before proliferation of hepatic progenitors
• accumulation of hepatic progenitor cells in the periductal region of livers from 9-12 months of age
• liver shows multiple layers of progenitor cells surrounding a single layer of ductal cells which show high mitotic activity after 9 months of age
|
|
• mutants exhibit enlarged, whitish livers containing large fat vacuoles by 12 weeks of age
(J:171445)
• mutants treated with rapamycin show reduced hepatocyte cell size, thus reducing the liver:body weight ratio
(J:171445)
|
|
• increase in glycogen storage in the liver
|
|
• 3-fold increase in triglyceride content in the liver
(J:88441)
• however, normal levels of plasma triglycerides
(J:88441)
• 2-4-fold increase of triglyceride content in the liver of 1 and 3 month old mutants, respectively
(J:160759)
|
|
• progressive development of fatty liver
(J:88441)
|
|
|
|
(J:218587)
|
|
• mutants exhibit enlarged, whitish livers containing large fat vacuoles by 12 weeks of age
• mutants treated with rapamycin exhibit no differences in steatosis compared to vehicle-treated mutants
|
|
|
• tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma
|
|
|
• mice develop liver tumors starting at approximately 8-9 months of age
• 50% of mice develop tumors between 9 and 12 months of age and 100% develop tumors by 12 months of age
• tumors show mixed cell characteristics, with tumors composed of colangiocytes, hepatocytes, and bi-lineage cells
|
|
|
• tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma
|
|
• 50% reduction in total body fat content
|
|
• decrease in fasting glucose levels at 1 and 3 months of age, however at 6 months of age, when severe steatosis is seen, the fasting glucose level is similar to wild-type
|
|
• decrease in fasting plasma insulin levels at 3 and 6 months of age
|
|
• decrease in serum leptin levels at one month of age
• however eating behavior is normal
|
|
|
• serum alanine aminotransferase levels increase progressively, reaching 5-fold higher levels at 12 months of age
|
|
• increase in glucose clearance during an intraperitoneal glucose load
|
|
• increase in glycogen storage in the liver
|
|
• increase in insulin sensitivity in the liver
|
|
• hepatocyte fatty acid uptake by passive diffusion is increased by 20% compared to controls, however active transportation of fatty acid is not changed and thus total fatty acid uptake is not significantly altered
• rate of fatty acid synthesis is 2.5-fold higher in mutant livers than in controls
|
|
• 30% decrease in circulating free fatty acids
|
|
• 3-fold increase in triglyceride content in the liver
(J:88441)
• however, normal levels of plasma triglycerides
(J:88441)
• 2-4-fold increase of triglyceride content in the liver of 1 and 3 month old mutants, respectively
(J:160759)
|
|
• decrease in lipolysis rate
|
|
• mutants exhibit enlarged, whitish livers containing large fat vacuoles by 12 weeks of age
(J:171445)
• mutants treated with rapamycin show reduced hepatocyte cell size, thus reducing the liver:body weight ratio
(J:171445)
|
|
|
• progressive hepatocyte cell death as mice progress from steatosis to premalignancy, with massive hepatocyte death by 9 months of age
|
|
|
• at 12 months of age, livers show increased cell proliferation
|
|
|
• marker analysis indicates oxidative stress in the liver
|
|
|
• tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma
|
|
|
• mice develop liver tumors starting at approximately 8-9 months of age
• 50% of mice develop tumors between 9 and 12 months of age and 100% develop tumors by 12 months of age
• tumors show mixed cell characteristics, with tumors composed of colangiocytes, hepatocytes, and bi-lineage cells
|
|
|
• tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hepatocellular carcinoma | DOID:684 |
OMIM:114550 |
J:218587 | |
| steatotic liver disease | DOID:9452 |
OMIM:228100 |
J:216841 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• in doxycycline-treated mice
|
|
|
• in doxycycline-treated mice
|
|
|
• in doxycycline-treated mice
|
|
|
• doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdpk1tm1Dral homozygotes
|
|
|
• doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdpk1tm1Dral homozygotes
|
|
|
• in doxycycline-treated mice
|
|
|
• in doxycycline-treated mice
|
|
|
• in doxycycline-treated mice
|
|
|
• doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdpk1tm1Dral homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• in doxycycline-treated mice
|
|
|
• in doxycycline-treated mice
|
|
|
• in doxycycline-treated mice
|
|
|
• doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdk1tm1Dral homozygotes
|
|
|
• doxycycline-treated mice exhibit increased proliferation in the prostate gland compared to in Pdk1tm1Dral homozygotes
|
|
|
• doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdk1tm1Dral homozygotes
|
|
|
• in doxycycline-treated mice
|
|
|
• in doxycycline-treated mice
|
|
|
• in doxycycline-treated mice
|
|
|
• doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdk1tm1Dral homozygotes
|
|
|
• doxycycline-treated mice exhibit increased proliferation in the prostate gland compared to in Pdk1tm1Dral homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• most mice die before 1 year of age
|
|
|
• large
|
|
|
• invasive with metastasis into the prostate stroma and urogenital area
|
|
|
• invasive with metastasis into the prostate stroma and urogenital area
|
|
|
• large
|
|
|
• invasive with metastasis into the prostate stroma and urogenital area
|
|
|
• large
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• regions of invasive prostate adenocarcinoma in mice over 1 year of age
|
|
N |
• mice survive at least 1 year
|
|
|
• regions of invasive prostate adenocarcinoma in mice over 1 year of age
|
|
|
• regions of invasive prostate adenocarcinoma in mice over 1 year of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with tamoxifen to induce cre-recombination exhibit an increase in white matter volume
|
|
• many axons in the corpus callosum are hypermyelinated when mice are treated with tamoxifen to induce cre-recombination
|
|
• increase in myelin sheath thickness
• outfoldings of the myelin sheaths in CNS and PNS are observed
|
|
• axons in the optic nerve are hypermyelinated when mice are treated with tamoxifen to induce cre-recombination
|
|
• many axons in the corpus callosum and optic nerve are hypermyelinated when mice are treated with tamoxifen to induce cre-recombination
• normally nonmyelinated C-fiber axons are spirally enwrapped by Remak Schwann cells are seen in mice treated with tamoxifen to induce cre-recombination
|
|
• axons in the optic nerve are hypermyelinated when mice are treated with tamoxifen to induce cre-recombination
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• mice survive at least 1 year
|
|
|
• mice exhibit microinvasive tumors in the prostate gland unlike in Pdpk1tm1Dral homozygotes
(J:170965)
• mutants develop castrate-resistant prostate cancer
(J:172730)
• mice develop intracystic prostatic carcinomas between 4 and 10 months of age
(J:268934)
|
|
|
• mice predominately develop adenocarcinoma localized to the dorsolateral lobes of the prostate
(J:184935)
• localized lesions that slowly progress to prostate adenocarcinomas
(J:212219)
• 4 of 8 mice develop prostatic adenocarcinoma and 3 of 8 mice exhibit invasive carcinomas after 10 months
(J:268934)
|
|
|
• in lesions, basal cells are not disorganized in contrast to Tg(Pbsn-ERG*)1Vv mice at 7 weeks
(J:131932)
• localized lesions that slowly progress to prostate adenocarcinomas
(J:212219)
• 4 of 4 mice develop low grade pancreatic intraepithelial neoplasia (PIN) and 2 of 4 mice show multifocal high grade PIN before 4 months of age
(J:268934)
• 6 of 6 mice exhibit multifocal high grade PIN at 4-10 months of age
(J:268934)
|
|
|
• mice exhibit microinvasive tumors in the prostate gland unlike in Pdpk1tm1Dral homozygotes
(J:170965)
• mutants develop castrate-resistant prostate cancer
(J:172730)
• mice develop intracystic prostatic carcinomas between 4 and 10 months of age
(J:268934)
|
|
|
• mice predominately develop adenocarcinoma localized to the dorsolateral lobes of the prostate
(J:184935)
• localized lesions that slowly progress to prostate adenocarcinomas
(J:212219)
• 4 of 8 mice develop prostatic adenocarcinoma and 3 of 8 mice exhibit invasive carcinomas after 10 months
(J:268934)
|
|
|
• in lesions, basal cells are not disorganized in contrast to Tg(Pbsn-ERG*)1Vv mice at 7 weeks
(J:131932)
• localized lesions that slowly progress to prostate adenocarcinomas
(J:212219)
• 4 of 4 mice develop low grade pancreatic intraepithelial neoplasia (PIN) and 2 of 4 mice show multifocal high grade PIN before 4 months of age
(J:268934)
• 6 of 6 mice exhibit multifocal high grade PIN at 4-10 months of age
(J:268934)
|
|
|
• prostate cancer metastasis after 10 months of age, with 12.5% of mice showing metastatic lesions to lungs and lymph nodes
|
|
|
• 2 of 6 mice develop intracystic prostatic carcinomas between 4 and 10 months of age
• 6 of 8 mice show intracystic prostatic carcinoma after 10 months of age
|
|
|
• mice exhibit microinvasive tumors in the prostate gland unlike in Pdpk1tm1Dral homozygotes
(J:170965)
• mutants develop castrate-resistant prostate cancer
(J:172730)
• mice develop intracystic prostatic carcinomas between 4 and 10 months of age
(J:268934)
|
|
|
• mice predominately develop adenocarcinoma localized to the dorsolateral lobes of the prostate
(J:184935)
• localized lesions that slowly progress to prostate adenocarcinomas
(J:212219)
• 4 of 8 mice develop prostatic adenocarcinoma and 3 of 8 mice exhibit invasive carcinomas after 10 months
(J:268934)
|
|
|
• in lesions, basal cells are not disorganized in contrast to Tg(Pbsn-ERG*)1Vv mice at 7 weeks
(J:131932)
• localized lesions that slowly progress to prostate adenocarcinomas
(J:212219)
• 4 of 4 mice develop low grade pancreatic intraepithelial neoplasia (PIN) and 2 of 4 mice show multifocal high grade PIN before 4 months of age
(J:268934)
• 6 of 6 mice exhibit multifocal high grade PIN at 4-10 months of age
(J:268934)
|
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:172730 , J:184935 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice develop invasive carcinoma in both the dorsolateral and anterior lobes of the prostate as early as 4 weeks with poorly differentiated carcinoma by 10 weeks
• marker analysis indicates that prostatic epithelial cells undergo epithelial-to-mesenchymal transition and that tumors exhibit a human metastatic prostate cancer signature
|
|
|
• mice develop macrometastatic lesions in the lung and liver with 100% penetrance
|
|
|
• early lethality, with mice dying between around 10 and 30 weeks of age
|
|
|
• prostates show an expansion of the leukemia stem cell (LSC)high subpopulation of stem/progenitor cells
• both the LSChigh (basal cell population) and LSClow (luminal cell population) subpopulations show enhanced sphere-forming in vitro
|
|
|
• mice develop invasive carcinoma in both the dorsolateral and anterior lobes of the prostate as early as 4 weeks with poorly differentiated carcinoma by 10 weeks
• marker analysis indicates that prostatic epithelial cells undergo epithelial-to-mesenchymal transition and that tumors exhibit a human metastatic prostate cancer signature
|
|
|
• prostates show an expansion of the leukemia stem cell (LSC)high subpopulation of stem/progenitor cells
• both the LSChigh (basal cell population) and LSClow (luminal cell population) subpopulations show enhanced sphere-forming in vitro
|
|
|
• mice develop invasive carcinoma in both the dorsolateral and anterior lobes of the prostate as early as 4 weeks with poorly differentiated carcinoma by 10 weeks
• marker analysis indicates that prostatic epithelial cells undergo epithelial-to-mesenchymal transition and that tumors exhibit a human metastatic prostate cancer signature
|
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:184935 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• lethality around 40 weeks of age
|
|
|
• mice develop focal neoplastic expansions in the prostate by 10 weeks and invasive carcinoma by 20 weeks
|
|
|
• mice develop macrometastatic lesions in the lung and liver with 100% penetrance
|
|
|
• mice develop focal neoplastic expansions in the prostate by 10 weeks and invasive carcinoma by 20 weeks
|
|
|
• mice develop focal neoplastic expansions in the prostate by 10 weeks and invasive carcinoma by 20 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:184935 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• one mouse at 6 weeks of age shows a microinvasive adenocarcinoma
• mice fed a high-fat diet upon weaning show an increase in the penetrance and number of microinvasive foci of microinvasive adenocarcinoma
|
|
|
• mice show a similar number of prostate ductules affected by intraepithelial neoplasia (mPIN) as single Ptentm1Hwu conditional mice
|
|
|
• one mouse at 6 weeks of age shows a microinvasive adenocarcinoma
• mice fed a high-fat diet upon weaning show an increase in the penetrance and number of microinvasive foci of microinvasive adenocarcinoma
|
|
|
• mice show a similar number of prostate ductules affected by intraepithelial neoplasia (mPIN) as single Ptentm1Hwu conditional mice
|
|
|
• one mouse at 6 weeks of age shows a microinvasive adenocarcinoma
• mice fed a high-fat diet upon weaning show an increase in the penetrance and number of microinvasive foci of microinvasive adenocarcinoma
|
|
|
• mice show a similar number of prostate ductules affected by intraepithelial neoplasia (mPIN) as single Ptentm1Hwu conditional mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increase in number CD45+ leukocytes in prostate tissue as compared to control (lacking JAG1 over expression)
• prostate tissue in 15/16 mutant mice contains large papillary structures with complex glandular architecture
• blood vessel density in prostate is 1.8 fold more than in control
• increased collagen deposition at the prostatic peri-glandular spaces
• presence of reactive stroma
• stromal cell layer is disrupted and thinner with increased vimentin staining in peri-glandular stromal cells
• prostate tissues contain more inflammatory foci as compared to controls (lacking JAG1 overexpression)
|
|
• 62.5% mutant mice (as compared to 20% in controls lacking JAG1 overexpression) have a mass of poorly differentiated adenocarcinoma extended into lumen of seminal vesicles and replacing the normal lining of epithelium
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
|
|
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
• mice develop a higher grade reactive stroma with lymphocytic infiltration as compared to control (lacking JAG1 overexpression)
|
|
• 62.5% mutant mice (as compared to 20% in controls lacking JAG1 overexpression) have a mass of poorly differentiated adenocarcinoma extended into lumen of seminal vesicles and replacing the normal lining of epithelium
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
|
|
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
• mice develop a higher grade reactive stroma with lymphocytic infiltration as compared to control (lacking JAG1 overexpression)
|
|
• increase in number CD45+ leukocytes in prostate tissue as compared to control (lacking JAG1 over expression)
• prostate tissue in 15/16 mutant mice contains large papillary structures with complex glandular architecture
• blood vessel density in prostate is 1.8 fold more than in control
• increased collagen deposition at the prostatic peri-glandular spaces
• presence of reactive stroma
• stromal cell layer is disrupted and thinner with increased vimentin staining in peri-glandular stromal cells
• prostate tissues contain more inflammatory foci as compared to controls (lacking JAG1 overexpression)
|
|
• 62.5% mutant mice (as compared to 20% in controls lacking JAG1 overexpression) have a mass of poorly differentiated adenocarcinoma extended into lumen of seminal vesicles and replacing the normal lining of epithelium
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
|
|
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
• mice develop a higher grade reactive stroma with lymphocytic infiltration as compared to control (lacking JAG1 overexpression)
|
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:238768 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
|
|
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
• prostate tissue in 2/8 mutant mice contains large papillary structures with complex glandular architecture
• mice develop a lower grade reactive stroma with lymphocytic infiltration as compared to mice with JAG1 overexpression
|
|
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
|
|
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
• prostate tissue in 2/8 mutant mice contains large papillary structures with complex glandular architecture
• mice develop a lower grade reactive stroma with lymphocytic infiltration as compared to mice with JAG1 overexpression
|
|
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
|
|
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
• prostate tissue in 2/8 mutant mice contains large papillary structures with complex glandular architecture
• mice develop a lower grade reactive stroma with lymphocytic infiltration as compared to mice with JAG1 overexpression
|
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:238768 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival of majority of mice is 10-20 weeks after intrabursal injection of an adenovirus expressing Cre
|
|
• 43% of ovarian tumors metastasize to the lungs
|
|
|
• 7 weeks after intrabursal injection through the infundibulum of an adenovirus expressing Cre, mice, mutants develop endometrioid ovarian cancer
• primary tumor is located in the ovary
• tumors are solid and cystic and diagnosed as ovarian edometrioid adenocarcinomas
|
|
|
• 7 weeks after intrabursal injection through the infundibulum of an adenovirus expressing Cre, mice, mutants develop endometrioid ovarian cancer
• primary tumor is located in the ovary
• tumors are solid and cystic and diagnosed as ovarian edometrioid adenocarcinomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:96296 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mutants exhibit premature activation of the entire primordial follicle pool with an enhanced rate of oocyte growth and follicular development greater than in either single mutant
|
|
|
• mutants exhibit premature activation of the entire primordial follicle pool with an enhanced rate of oocyte growth and follicular development greater than in either single mutant
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mutant females exhibit accelerated activation of primordial follicles
|
|
|
• mutant females exhibit accelerated activation of primordial follicles
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• fertility of double mutant females is completely restored from 10-30 weeks of age when mated with wild-type males compared to single conditional homozygous Pdpk1 mutants
• embryos derived from double mutant females mated with wild-type males show normal perimplantation development, indicating rescue of the two-cell arrest and the suppressed embryonic genome activation seen in embryos from single conditional homozygous Pdpk1 mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 40% of mice survive weaning if littermate competition is removed and the weaning period is extended
|
|
• mice that survive weaning do not live beyond 250 days
• however, survival can be increased by treatment with rapamycin
|
|
• mice die rapidly in the first few days of life
• however, lifespan can be increased if littermate competition is removed and the weaning period is extended
|
|
• 11% of mice exhibit thoracic and abdominal/inguinal mammary gland tumors
• mammary gland tumors exhibit prominent intraluminal and ductal proliferation
• mammary gland tumors ranged from fibroadenomas to adenocarcinomas and ductal carcinomas with dense hyaline collagen or dense fibrosis
|
|
• 12% of mice develop thyroid tumors with a follicular aspect
|
|
• mice develop multiple hyperproliferative skin lesions that range from mucocutaneous lesions to tumor formation
|
|
• mice develop papules around the nose, mouth and eyes
|
|
• 56% of mice develop multinodular goiters
|
|
|
• in 80% of mice
|
|
• 11% of mice exhibit thoracic and abdominal/inguinal mammary gland tumors
• mammary gland tumors exhibit prominent intraluminal and ductal proliferation
• mammary gland tumors ranged from fibroadenomas to adenocarcinomas and ductal carcinomas with dense hyaline collagen or dense fibrosis
|
|
• 12% of mice develop thyroid tumors with a follicular aspect
|
|
|
• in 80% of mice
|
|
• 11% of mice exhibit thoracic and abdominal/inguinal mammary gland tumors
• mammary gland tumors exhibit prominent intraluminal and ductal proliferation
• mammary gland tumors ranged from fibroadenomas to adenocarcinomas and ductal carcinomas with dense hyaline collagen or dense fibrosis
|
|
• at 11 days, the hair shafts have a disheveled appearance unlike in heterozygous mice
|
|
• hair follicles are increased in size compared to in wild type mice
|
|
• facial and periauricular lesions involve hyperproliferation of the outer root sheath in the vibrissae
|
|
• papillomatous lesions of the skin exhibit hyperkeratosis and acanthosis through the face and body skin
|
|
• papillomatous lesions of the skin exhibit hyperkeratosis and acanthosis through the face and body skin
|
|
• at 6 days of age
|
|
• mice develop multiple hyperproliferative skin lesions that range from mucocutaneous lesions to tumor formation
• facial and periauricular lesions involve hyperproliferation of the outer root sheath and vibrissae
• acral extremities areas exhibit verrucous and hyperkeratotic lesions also seen in the punctuate palmoplantar keratosis of the paws
• mice exhibit palmoplantar keratoses, acral keratosis and oral papules
• cutaneous lesions contain trichilemmomas
• however, rapamycin treatment reverses and prevents lesion formation
|
|
• at 6 days of age
|
|
• mice develop multiple hyperproliferative skin lesions that range from mucocutaneous lesions to tumor formation
|
|
• mice develop papules around the nose, mouth and eyes
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Cowden syndrome | DOID:6457 |
OMIM:PS158350 |
J:138927 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit decreased survival compared to wild type mice
|
|
• 36% of mice exhibit thoracic and abdominal/inguinal mammary gland tumors
• mammary gland tumors exhibit prominent intraluminal and ductal proliferation
• mammary gland tumors ranged from fibroadenomas to adenocarcinomas and ductal carcinomas with dense hyaline collagen or dense fibrosis
|
|
• 36% of mice exhibit thoracic and abdominal/inguinal mammary gland tumors
• mammary gland tumors exhibit prominent intraluminal and ductal proliferation
• mammary gland tumors ranged from fibroadenomas to adenocarcinomas and ductal carcinomas with dense hyaline collagen or dense fibrosis
|
|
• 36% of mice exhibit thoracic and abdominal/inguinal mammary gland tumors
• mammary gland tumors exhibit prominent intraluminal and ductal proliferation
• mammary gland tumors ranged from fibroadenomas to adenocarcinomas and ductal carcinomas with dense hyaline collagen or dense fibrosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• transplanted mammary epithelium exhibits more and feather-like irregular side-branches in ductal and terminal structures compared with controls
|
|
|
• transplants from virgins exhibit focal ductal hyperplasia containing papillary structure
• after one pregnancy, transplants exhibit intra-luminal focal hyperplasia
|
|
|
• transplanted mammary epithelium exhibits more and feather-like irregular side-branches in ductal and terminal structures compared with controls
|
|
|
• transplants from virgins exhibit focal ductal hyperplasia containing papillary structure
• after one pregnancy, transplants exhibit intra-luminal focal hyperplasia
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Cowden syndrome | DOID:6457 |
OMIM:PS158350 |
J:78415 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in mice fed a normal diet, the weights of injured tibialis anterior muscles are greater than weights of muscles in controls
• regenerating myofibers after injury are larger compared to control injured myofibers, indicating that mutants exhibit a promotion in regeneration of injured muscles
• after 8 months of a high-fat diet, mutants exhibit larger myofiber sizes of regenerating muscles at 6 and 12 days after injury and increased weights of the injured tibialis anterior muscles than controls
• after 8 months on a high-fat diet, collagen deposition is reduced in regenerating muscles compared to controls
|
|
• after 8 months of a high-fat diet, mutants exhibit lower glucose levels than controls on the same diet
|
|
• after 8 months of a high-fat diet, mutants exhibit lower insulin levels than controls on the same diet
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• die shortly after birth
|
|
• cells from mutant brains are larger
|
|
• increase in cell proliferation in the ventricular zone of E14.5 mutant telencephalon
• decrease in cell death in the ventricular zone of E14.5 mutant telencephalon
|
|
• brain weight is increased at E14, E18, and at birth
• brain weight at birth is double that of wild-type
|
|
• nuclei in the brainstem are not identifiable
|
|
• the laminar pattern of the hippocampus is disturbed
|
|
• the laminar pattern of the cerebellum is disturbed
|
|
• cortex cells from E14.5 brains cultured at moderate or clonal density exhibit a significantly greater number of neurospheres than wild-type cells, indicating an increase in stem/progenitor cells in mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• only 45% of males survive to 13.5 months of age, compared to 75% of females surviving to this age
|
|
|
• hyperplasia in the anterior prostate is observed at 8 days of age
|
|
|
• within the first year of life, 97% of males develop tumors of the anterior prostate
• prostate tumors are carcinomas
• in males over one year of age, the tumor takes over the entire prostate and seminal vesicle
|
|
• hyperplasia in the urinary tract
|
|
• urothelial carcinoma of the kidney
|
|
• urothelial carcinoma of the bladder
• 22% of mutants exhibit bladder cancer by 13.5 months of age
|
|
• males exhibit hydronephrosis of the kidney
|
|
• epithelial hypertrophy and nuclear atypia are evident in bladders at birth
• 100% penetrance of hypertrophy and hyperplasia in the bladder by 6 weeks of age
|
|
|
• 1/3 of male deaths are due to inability to urinate due to urinary tract blockage
• females do not lose the ability to urinate
|
|
|
• hyperplasia in the anterior prostate is observed at 8 days of age
|
|
|
• within the first year of life, 97% of males develop tumors of the anterior prostate
• prostate tumors are carcinomas
• in males over one year of age, the tumor takes over the entire prostate and seminal vesicle
|
|
|
• within the first year of life, 97% of males develop tumors of the anterior prostate
• prostate tumors are carcinomas
• in males over one year of age, the tumor takes over the entire prostate and seminal vesicle
|
|
• metastasis of the bladder and urothelial carcinomas is observed
|
|
• urothelial carcinoma of the bladder, ureter, and kidney
• squamous cell carcinoma of the vagina and rectum
• carcinomas of the prostate, seminal vesicles and urethra
|
|
• urothelial carcinoma of the kidney
|
|
• 41% of females develop vaginal squamous cell carcinoma
|
|
• urothelial carcinoma of the bladder
• 22% of mutants exhibit bladder cancer by 13.5 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 42% of mutants develop skin papillomas
|
|
• 42% of mutants develop skin papillomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• hearts of mutants treated with tamoxifen for 3 weeks to induce cre-expression develop significantly better function recovery in response to 30 min ischemia followed by 120 min reperfusion than controls, showing significantly improved end-diastolic pressure, left ventricle developed pressure (LVDP) and LVDP recoveries, and improved systolic and diastolic contractility of hearts
• at 60 min post reperfusion, recovery of left ventricular diastolic pressure reaches 77.9% of pre-ischemia in hearts versus 44% in controls
• hearts have significantly fewer apoptosis positive cardiomyocytes after ischemia/reperfusion (I/R) injury than controls
|
|
• mutants treated with tamoxifen to induce cre-expression exhibit a significant reduction in infarct size after ischemia
|
|
• hearts of mutants treated with tamoxifen for 3 weeks to induce cre-expression develop significantly better function recovery in response to 30 min ischemia followed by 120 min reperfusion than controls, showing significantly improved end-diastolic pressure, left ventricle developed pressure (LVDP) and LVDP recoveries, and improved systolic and diastolic contractility of hearts
• at 60 min post reperfusion, recovery of left ventricular diastolic pressure reaches 77.9% of pre-ischemia in hearts versus 44% in controls
• hearts have significantly fewer apoptosis positive cardiomyocytes after ischemia/reperfusion (I/R) injury than controls
|
|
• mutants treated with tamoxifen to induce cre-expression exhibit a significant reduction in infarct size after ischemia
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• death occurs around P21
|
|
• cerebella layering defects
• before P3, cerebella are enlarged but the external granule layer (EGL) and cerebellar lobules are normal and Purkinje cell position is normal
• however, after P6, mutants show a marked cerebellar enlargement and lack internal granule layer and folia
|
|
• loss of foliation after P6
|
|
• Purkinje layer defect is first seen at P4-P6 and by P9, numerous Purkinje neurons are randomly scattered
|
|
• disruption of Bergmann glial layering
|
|
• premature differentiation of Bergmann glia leading to extensive layering defects
|
|
• some Bergmann cell bodies are randomly distributed at P7 and lose their contacts to the pial surface and are positioned deep within the internal granule layer region
|
|
• Purkinje cell layer is normal at P3 but there are many ectopic Purkinje cells by P9
|
|
• lack of an organized internal granule layer (IGL) at P6
• severe granule neuron layering defects
|
|
• mutants exhibit granule neuron migration defects, with granule neurons failing to migrate to the internal granule layer and accumulating in the molecular layer (ML)
• granule neurons are resistant to low potassium-induced cell death under serum deprivation conditions
|
|
• premature differentiation of Bergmann glia leading to extensive layering defects
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• ovaries are enlarged by P21 due to global primordial follicle activation
|
|
|
• ovaries explanted at birth and cultured for 8 days grow more rapidly than controls
|
|
|
• ovaries are enlarged by P21 due to global primordial follicle activation
|
|
|
• ovaries explanted at birth and cultured for 8 days grow more rapidly than controls
|
|
|
• females exhibit a dramatic age-dependent decrease in fertility and have no more than two litters
|
|
|
• ovaries are enlarged by P21 due to global primordial follicle activation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants infected with lymphocytic choriomeningitis virus (LCMV) to induce T-cell activation and thus cre-expression exhibit better survival of effector CD8 T cells under serum-starvation conditions compared to controls, but only show modest effects on the expansion and contraction of effector CD8 T cells
• clonal burst of mutant effector CD8 T cells is about 1/2 that of wild-type controls and there is a slight, but not significant reduction in the number of memory T cells that form in lymphoid and nonlymphoid tissues
|
|
• production of IL-2 by CD8 T cells is diminished in mutants infected with LCMV to induce T-cell activation and thus cre-expression
|
|
• mutants infected with lymphocytic choriomeningitis virus (LCMV) to induce T-cell activation and thus cre-expression exhibit better survival of effector CD8 T cells under serum-starvation conditions compared to controls, but only show modest effects on the expansion and contraction of effector CD8 T cells
• clonal burst of mutant effector CD8 T cells is about 1/2 that of wild-type controls and there is a slight, but not significant reduction in the number of memory T cells that form in lymphoid and nonlymphoid tissues
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 10 of 23 mutants between 2-11 months of age exhibit varying degrees of hyperplasia primarily in larger bile duct
|
|
• 10 of 23 mutants between 2-11 months of age exhibit varying degrees of hyperplasia primarily in larger bile duct
|
|
• 6 of 15 mutants between 12-16 months of age have cholangiocellular carcinoma foci, although much fewer of them and smaller ones than in double Smad4 and Pten mutants, and no invasive cholangiocelluar carcinomas were seen
|
|
• 1 of 13 and 5 of 15 mutants develop hepatocellular carcinoma at 8-9 months of age and 12-16 months of age, respectively
|
|
• 6 of 15 mutants between 12-16 months of age have cholangiocellular carcinoma foci, although much fewer of them and smaller ones than in double Smad4 and Pten mutants, and no invasive cholangiocelluar carcinomas were seen
|
|
• 1 of 13 and 5 of 15 mutants develop hepatocellular carcinoma at 8-9 months of age and 12-16 months of age, respectively
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• enlarged in a smooth and symmetrical manner with abundant colloid
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pioglitazone-fed mice exhibit lipid accumulation in thyroid cells
|
|
• 100-fold increase in size
• larger than in Ptentm1Hwu/Ptentm1Hwu Tg(TPO-cre)1Shk mice
• irregularly shaped, mutlinodular, more cellular than colloid
• however, pioglitazone (a PPARG inhibitor) decreases thyroid size
|
|
• with metastasis to the lungs and soft tissues
• however, pioglitazone (a PPARG inhibitor) induces a lipogenic antitumor response
|
|
• pioglitazone-fed mice exhibit decreased thyroid size due to increased apoptosis
|
|
• 6-fold
• however, pioglitazone normalizes thyroid function
|
|
• 3.5-fold
• however, pioglitazone normalizes thyroid function
|
|
• with metastasis to the lungs and soft tissues
• however, pioglitazone (a PPARG inhibitor) induces a lipogenic antitumor response
|
|
• pioglitazone-fed mice exhibit decreased thyroid size due to increased apoptosis
|
|
• pioglitazone-fed mice exhibit decreased thyroid size due to increased apoptosis
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| thyroid gland carcinoma | DOID:3963 | J:177181 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• epithelial hyperplasia in vesicular glands
|
|
• genital tissues are enlarged
|
|
|
• epithelial hyperplasia in vesicular glands
|
|
|
• endometrial hyperplasia is accompanied by partial squamous differentiation
|
|
|
• hyperplasia of the endometrial glands and lumen
|
|
|
• epithelial hyperplasia in epididymis
|
|
|
• epithelial hyperplasia in vas deferens
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• tumors contain regions of cystadenoma characterized by adenoid structures identical to human cystadenoma lesions arising in epididymides
• cystadenoma display clear cell morphology
|
|
|
• cysts and squamous epithelial hyperplasia in the oviduct
|
|
|
• females exhibit hyperplasia and full squamous differentiation of the uterine endometrial lumen, endometrial hyperplasia, and endometrial hyperplasia with cyst formation
|
|
|
• cysts and squamous epithelial hyperplasia in the cervix
|
|
|
• squamous metaplasia is seen in the epididymis
• vascularization is increased in the epididymides
|
|
• regions of squamous differentiation intermingle with the regions of cystadenoma
• cystadenomas appear to result from basal cell proliferation without differentiation, whereas regions of squamous metaplasia contain abundant basal cells in basal layers as well as cells with markers of epidermal differentiation
|
|
• all mutants develop benign mixed adenosquamous genital tract tumors (in epididymis, vesicular glands, vas deferens, endometrium, and oviduct) resembling clear cell cystadenomas that form in patients with Von Hippel-Lindau syndrome (VHL)
• tumors arise simultaneously in all genital tract epithelia and show expansion of basal cells
• endometrial hyperplasia with cyst formation resembles cystadenoma and cystic lesions seen in broad ligament of females with VHL
|
|
|
• tumors contain regions of cystadenoma characterized by adenoid structures identical to human cystadenoma lesions arising in epididymides
• cystadenoma display clear cell morphology
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| von Hippel-Lindau disease | DOID:14175 |
OMIM:193300 |
J:137442 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival is 85 days following injection of PDGF and cre compared with 27 days for similarly treated Ptentm1Hwu Trp53tm1Thl double homozygotes
|
|
• following injection of PDGF and cre, all mice develop glioblastoma composed of oligodendrocyte progenitor cells
|
|
• following injection of PDGF and cre, all mice develop glioblastoma composed of oligodendrocyte progenitor cells
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| glioblastoma proneural subtype | DOID:0050804 | J:172585 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival is 27 days following injection of PDGF and cre compared with 85 days for similarly treated Ptentm1Hwu homozygotes
|
|
• following injection of PDGF and cre, tumor growth is increased compared to in similarly treated Ptentm1Hwu homozygotes
|
|
• following injection of PDGF and cre, all mice develop glioblastoma composed of oligodendrocyte progenitor cells
|
|
• following injection of PDGF and cre, all mice develop glioblastoma composed of oligodendrocyte progenitor cells
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| glioblastoma proneural subtype | DOID:0050804 | J:172585 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no mice surviving tumor-free beyond 15 weeks following intracranial injection of an adenoviral cre unlike similarly treated Col1a1tm2(CAG-EGFR*)Char or Col1a1tm1(CAG-EGFR)Char homozygotes that do not develop tumors
|
|
• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with no mice surviving tumor-free beyond 13 weeks unlike similarly treated Col1a1tm2(CAG-EGFR*)Char or Col1a1tm1(CAG-EGFR)Char homozygotes that do not develop tumors
|
|
• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with no mice surviving tumor-free beyond 13 weeks unlike similarly treated Col1a1tm2(CAG-EGFR*)Char or Col1a1tm1(CAG-EGFR)Char homozygotes that do not develop tumors
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| high grade glioma | DOID:3070 |
OMIM:PS137800 |
J:146494 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 10% of mice die from glioblastoma multiforme development following intracranial injection of an adenoviral cre unlike similarly treated Col1a1tm1(CAG-EGFR)Char homozygotes that do not develop tumors
|
|
• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with a greater than 90% tumor-free survival past 30 weeks unlike similarly treated Col1a1tm1(CAG-EGFR)Char homozygotes that do not develop tumors
|
|
• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with a greater than 90% tumor-free survival past 30 weeks unlike similarly treated Col1a1tm1(CAG-EGFR)Char homozygotes that do not develop tumors
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| high grade glioma | DOID:3070 |
OMIM:PS137800 |
J:146494 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no mice surviving tumor-free beyond 10 weeks following intracranial injection of an adenoviral cre unlike similarly treated Col1a1tm2(CAG-EGFR*)Char homozygotes that do not develop tumors
|
|
• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with no mice surviving tumor-free beyond 10 weeks unlike similarly treated Col1a1tm2(CAG-EGFR*)Char homozygotes that do not develop tumors
|
|
• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with no mice surviving tumor-free beyond 10 weeks unlike similarly treated Col1a1tm2(CAG-EGFR*)Char homozygotes that do not develop tumors
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| high grade glioma | DOID:3070 |
OMIM:PS137800 |
J:146494 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Ovary tumors in Pik3catm1.1Waph/Pik3catm1.1Waph Ptentm1Hwu/Ptentm1Hwu mice
|
• of mice infected with a cre-expressing adenovirus due to ovarian masses with a median latency of 16 weeks
• however, treatment with an ATP-competitive PI3K/mTOR inhibitor, PF04691502 extends survival time
|
|
|
• the ovarian surface epithelium of mice infected with a cre-expressing adenovirus exhibit marked hyperplasia compared with control mice
• mice infected with a cre-expressing adenovirus exhibit ovarian masses and show varying degrees of fibrous and/or smooth muscle hyperplasia compared with control mice
|
|
|
• mice infected with a cre-expressing adenovirus develop ovarian serous adenocarcinomas, ovarian granulosa cell tumors and a single ovarian luteoma compared with control mice
|
|
|
• mice infected with a cre-expressing adenovirus develop ovarian granulosa cell tumors compared with control mice
|
|
|
• mice infected with a cre-expressing adenovirus exhibit ovarian surface epithelium hyperproliferative changes compared with control mice
|
|
|
• mice infected with a cre-expressing adenovirus develop hemorrhagic ascites compared with control mice
|
|
|
• mice infected with a cre-expressing adenovirus develop ovarian serous adenocarcinomas, ovarian granulosa cell tumors and a single ovarian luteoma compared with control mice
|
|
|
• mice infected with a cre-expressing adenovirus develop ovarian granulosa cell tumors compared with control mice
|
|
• mice infected with a cre-expressing adenovirus develop ovarian serous adenocarcinomas compared with control mice
|
|
• mice infected with a cre-expressing adenovirus exhibit intraperitoneal masses on the peritoneal wall and diaphragm masses compared with control mice
|
|
• mice infected with a cre-expressing adenovirus develop hemorrhagic ascites compared with control mice
|
|
|
• mice infected with a cre-expressing adenovirus develop hemorrhagic ascites compared with control mice
|
|
|
• the ovarian surface epithelium of mice infected with a cre-expressing adenovirus exhibit marked hyperplasia compared with control mice
• mice infected with a cre-expressing adenovirus exhibit ovarian masses and show varying degrees of fibrous and/or smooth muscle hyperplasia compared with control mice
|
|
|
• mice infected with a cre-expressing adenovirus develop ovarian serous adenocarcinomas, ovarian granulosa cell tumors and a single ovarian luteoma compared with control mice
|
|
|
• mice infected with a cre-expressing adenovirus develop ovarian granulosa cell tumors compared with control mice
|
|
|
• mice infected with a cre-expressing adenovirus exhibit ovarian surface epithelium hyperproliferative changes compared with control mice
|
|
|
• mice infected with a cre-expressing adenovirus develop hemorrhagic ascites compared with control mice
|
|
• mice infected with a cre-expressing adenovirus exhibit intraperitoneal masses on the peritoneal wall and diaphragm masses compared with control mice
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
||
|
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support. |
last database update 04/23/2024 MGI 6.23 |
|
|
|
||