Analysis Tools|
Allele Symbol Allele Name Allele ID |
Smad5tm1Huy targeted mutation 1, Danny Huylebroeck MGI:2679441 |
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| Summary |
12 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mutants exhibit normal blood vessel development, normal blood vessel morphology in adults, normal angiogenesis, and a similar vascular remodeling response as controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 N |
• when 6-wk-old females (pretreated with estrogen at P21 and P22 to increase Ltf-icre activity) are mated with wild-type males for 6 months, female fertility is normal despite a slight reduction in average litter size and a slight increase in the time to first litter
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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N |
• females treated with estrogen at P21 and P22 (to increase Ltf-icre activity) show no defects in endometrial gland morphology or stromal cell compartments in the uterus at 16 weeks of age
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• females failed to produce any litters in month 5 or 6 of the breeding trial, indicating a gradual decline in fertility
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• at 6.5 dpc, the pregnancy rate is significantly lower than that in control females (12.5% versus 88.9%, respectively)
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• at 5.5 dpc, the extent of decidual development and decidual pSMAD1/5 expression are reduced in the implantation sites
• after induction of artificial decidualization, the ratio of the decidual to non-decidual uterine horn weight is significantly lower than that in controls, indicating defective stromal cell decidualization
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• at 4.5 dpc, unattached blastocysts are detected in the uterus
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• delayed embryo implantation appears to cause a subsequent cascade of defects that results in early pregnancy losses
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• at 4.5 dpc, females show a wide range of implantation defects, including loosely attached/floating blastocysts, decreased PTGS2 (aka COX2) expression, FOXO1 cytoplasmic mislocalization, and retained PR expression in the luminal uterine epithelium
• ~50% of females exhibit no implantation sites at 4.5 dpc, as detected by blue dye injection
• at 5.5 dpc, implantation sites show various morphological and molecular defects
• at 6.5 dpc, the number of implantation sites is decreased, and the few sites observed are smaller, appear to be growth restricted, and show reduced decidual development
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• at 3.5 dpc, the luminal uterine epithelium continues to proliferate and shows prominent Ki67 staining, increased MUC1 expression and enhanced E2-response, indicating a non-receptive state
• defective expression of various histological and molecular markers of endometrial receptivity is observed at 4.5 dpc
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• females failed to deliver any pups after the third month of the 6-mo fertility trial
• 4 of 7 females lost the ability to produce pups after the first litter
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• when 6-wk-old females (pretreated with estrogen at P21 and P22 to increase Ltf-icre activity) are mated with wild-type males, the total number of cumulative pups obtained over a 6-mo fertility trial is significantly lower than that in controls (35 versus 201 pups, respectively), indicating severe subfertility
• over the course of the trial, the number of pups per female is significantly lower than that in control females (5.13 +/- 3.56 versus 29.13 +/- 9.15 pups/female, respectively)
• however, the number of blastocysts collected at 3.5 dpc is not altered, indicating normal ovarian and oviductal function
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• over the course of a 6-mo fertility trial, number of pups per litter is significantly lower than that in control females (2.85 +/- 1.86 versus 6.61 +/- 1.55 pups/litter, respectively)
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• endometrial receptivity and implantation defects result in impaired decidual and embryonic development at 5.5 dpc and 6.5 dpc
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• at 5.5 dpc, the extent of decidual development and decidual pSMAD1/5 expression are reduced in the implantation sites
• after induction of artificial decidualization, the ratio of the decidual to non-decidual uterine horn weight is significantly lower than that in controls, indicating defective stromal cell decidualization
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• females failed to produce any litters in month 5 or 6 of the breeding trial, indicating a gradual decline in fertility
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• female mice become infertile after 3 to 4 months of breeding
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• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
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• over 70% of female mice have metastic ovarian cancer by 1 year of age
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• 100% of male mice by 7 months of age exhibit tumors in the testis
• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation
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• female mice become infertile after 3 to 4 months of breeding
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• slight infertility, with a 16% decrease in litters per month when bred to wild-type females
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• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
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• over 70% of female mice have metastic ovarian cancer by 1 year of age
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• 100% of male mice by 7 months of age exhibit tumors in the testis
• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation
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• found in 50% of female mice over 9 months in age
• found in about 60% of male mice by 11 months in age
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• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
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• over 70% of female mice have metastic ovarian cancer by 1 year of age
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• 100% of male mice by 7 months of age exhibit tumors in the testis
• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• female mice become infertile after 3 to 4 months of breeding
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• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
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• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
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|
• 100% of male mice by 7 months of age exhibit tumors in the testis
• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation
|
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• female mice become infertile after 3 to 4 months of breeding
|
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|
• slight infertility, with a 16% decrease in litters per month when bred to wild-type females
|
|
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• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
|
|
|
• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
|
|
• 100% of male mice by 7 months of age exhibit tumors in the testis
• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation
|
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• found in 50% of female mice over 9 months in age
• found in about 60% of male mice by 11 months in age
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• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
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|
• over 70% of female mice have metastic ovarian cancer by 1 year of age
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• 100% of male mice by 7 months of age exhibit tumors in the testis
• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 33% of mutant females survived to 32 weeks
• 50% survival at approximately 29 week of age
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• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
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• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
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• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:157310 | |
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 33% of mutant females survived to 32 weeks
• 50% survival at approximately 29 week of age
|
|
|
• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
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|
• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
|
|
|
• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:157310 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 33% of mutant females survived to 32 weeks
• 50% survival at approximately 29 week of age
|
|
|
• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
|
|
|
• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
|
|
|
• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)
• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level
• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:157310 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mutants exhibit normal blood vessel development and blood vessel morphology in adults
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mild dilation of the heart
• no cardiomyopathy, cardiac hypertrophy, or differences in heart rate and have normal blood vessel development, blood vessel morphology in adults, angiogenesis and vascular remodeling response
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• at 9 months of age, females, but not males, show larger systolic and diastolic LV internal diameters and decreased fractional shortening, indicating decreased cardiac contractility
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• females, but not males, perform worse in a treadmill experiment
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• at 9 months of age, females, but not males, show larger systolic and diastolic LV internal diameters and decreased fractional shortening, indicating decreased cardiac contractility
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• females, but not males, perform worse in a treadmill experiment
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
|
|
|
• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
|
|
• female mice become infertile after 3 to 4 months of breeding
|
|
|
• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
|
|
|
• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
|
|
• female mice become infertile after 3 to 4 months of breeding
|
|
|
• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors
|
|
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• over 70% of female mice have metastic ovarian cancer by 1 year of age
|
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• found in 50% of female mice over 9 months in age
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 11/12/2024 MGI 6.24 |
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