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Allele Symbol Allele Name Allele ID |
Rae1tm1Jvd targeted mutation 1, Jan M A van Deursen MGI:3619246 |
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| Summary |
5 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• homozygous embryos are present at E3.5 but absent by E8.5
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• in culture the inner cell mass fails to expand from E6.5 to E8.5 and instead degenerates
• however, the trophoblast cells develop normally
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in heterozygous MEFs after 5 passages about 20% of metaphases are aneuploid compared to about 9% in wild-type cells and a wider range of nonmodal chromosome numbers is seen
(J:81546)
• at 5 months of age, 9% of splenocytes are aneuploid
(J:81546)
• the number of aneuploid splenocytes increases from 9% at 5 months to 33% at 24 months compared to only 3% in wild-type mice at 35 months
(J:105717)
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• after 12 hours of treatment with 200 ng/ml nocodazole (induces spindle damage) only 2.5% of heterozygous MEFs are arrested compared to 15% of wild-type cells and after 4 hours in serum without nocodazole (recovery phase) more cells are present with 4N DNA content suggesting progression to G1 without cell division
(J:81546)
• overexpression of Rae1 can rescue the mitotic checkpoint defect
(J:81546)
• after nocodazole treatment the time for 50% of cells to exit prometaphase arrest is reduced to 3 hours compared to 7.2 hours for wild-type MEFs
(J:105717)
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• lagging chromosomes are seen in 5% of anaphase figures compared to 2% of wild-type figures
(J:81546)
• in splenocytes prematurely separated sister chromatids increase from 0 at 5 months to being present in 10-11% of metaphases at 24-27 months compared to 0 at 27 months and only 4% at 35 months in wild-type
(J:105717)
• however, no chromosome breaks or fusions are seen at 24 months of age
(J:105717)
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• a single application of 50 ul of 0.5% DMBA at P5 results in an increased incidence of lung tumors and more tumors per animal in heterozygotes compared to wild-type mice
• however, no difference in spontaneous tumor incidence is seen compared to wild-type mice
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• a single application of 50 ul of 0.5% DMBA at P5 results in an increased incidence of lung tumors and more tumors per animal in heterozygotes compared to wild-type mice
• however, no difference in spontaneous tumor incidence is seen compared to wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• chromosome segregation errors are reduced to 18% from 37% in double Rae1tm1Jvd Nup98tm1Jvd heterozygotes and the mitotic checkpoint is fully restored
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Reduced lifespan, cataract, lordokyphosis and cachexia in Bub3tm1Jvd/Bub3+ Rae1tm1Jvd/Rae1+ mice
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• seen in the second year of life
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• in double heterozygous MEFs after 5 passages aneuploid cells are increased by 32% compared to wild-type cells and a wider range of nonmodal chromosome numbers is seen compared to single heterozygous or wild-type MEFs
(J:81546)
• at 5 months of age, 37% of splenocytes are aneuploid compared to 9% in single heterozygotes
(J:81546)
• the number of aneuploid splenocytes increases from 37% at 5 months to 47% at 24 months compared to only 3% in wild-type mice at 35 months
(J:105717)
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• after nocodazole treatment the time for 50% of cells to exit prometaphase arrest is reduced to 2.2 hours compared to 7.2 hours for wild-type MEFs
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• prematurely separated sister chromatids are seen in 19% and 13% of mitotic figures from MEFs and splenocytes (at 5 months of age), respectively
(J:81546)
• lagging chromosomes are seen in 15% of anaphase figures compared to 5% of single heterozygous and 2% of wild-type figures
(J:81546)
• in splenocytes prematurely separated sister chromatids increase from 14% at 5 months to being present in 24% of metaphases at 24 months compared to 0 at 27 months and only 4% at 35 months in wild-type
(J:105717)
• however, no chromosome breaks or fusions are seen at 24 months of age
(J:105717)
• 47% of anaphases have multiple lagging chromosomes compared to 0% in wild-type MEFs
(J:105717)
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• double heterozygous MEFs grow slower than single heterozygous or wild-type MEFs
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• at passage 5 and 7 increased expression of senescence related genes in MEFs is seen
• at passage 7 but not passage 3, double heterozygous MEFs grow slower than single heterozygous or wild-type MEFs
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• decreased thickness of the subcutaneous adipose tissue
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• at 27 months of age a dramatic decrease in body fat is seen
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• body weight is similar to wild-type at 5 months of age but significantly lower by 24 months of age
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• clear signs of skeletal muscle degeneration and atrophy are seen in mice with lordokyphosis
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• clear signs of skeletal muscle degeneration and atrophy are seen in mice with lordokyphosis
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• lordokyphosis is seen at an earlier age and with increased severity compared to single heterozygous or wild-type mice
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• incidence of cataract formation is increased and the latency is decreased compared to single heterozygotes
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• a single application of 50 ul of 0.5% DMBA at P5 results in an increased incidence of lung tumors and more tumors per animal in double heterozygotes compared to wild-type mice
• however, no difference in spontaneous tumor incidence is seen compared to wild-type mice
|
|
• a single application of 50 ul of 0.5% DMBA at P5 results in an increased incidence of lung tumors and more tumors per animal in double heterozygotes compared to wild-type mice
• however, no difference in spontaneous tumor incidence is seen compared to wild-type mice
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• decreased thickness of the subcutaneous adipose tissue
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• from 5 to 27 months of age dermal thickness decreases by 21% lower compared a decrease of 9% in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• MEFs exhibit mitotic checkpoint defects
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• MEFs have increased rates of chromatin bridges and lagging chromosomes indicating chromosome segregation errors
• incomplete centrosome separation is increased in MEFs
• MEFs treated with the PLK1 inhibitor BI2536 show restoration of normal centrosome separation
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• MEFs exhibit more frequent spindle geometry defects showing mitotic spindle asymmetry
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/16/2024 MGI 6.23 |
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