Phenotypes associated with this allele
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bub1btm1Jvd mutation
(0 available);
any
Bub1b mutation
(58 available)
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mortality/aging
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• the median life span is about 6 months
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adipose tissue
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• at 12 months of age the subcutaneous fat cell layer is significantly thinner compared to wild-type mice
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• total body fat declines prematurely
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cellular
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• sperm counts are about 4 time lower than in wild-type mice
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• after nocodazole treatment the time for 50% of cells to exit prometaphase arrest is reduced to 1.1 hours compared to 7.2 hours for wild-type MEFs
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• 17% of anaphases have multiple lagging chromosomes compared to 0% in wild-type MEFs
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• senescence associated markers are increased in kidneys from 5 month old mutants compared to wild-type mice
(J:91128)
• the number of senescent cells is increased compared to wild-type MEFs or MEFs double heterozygous for Rae1tm1Jvd and Bub3tm1Jvd
(J:105717)
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• mild aneuploidy develops by 2 months and increases in degree and severity as the mice age
• despite the increase in aneuploidy only 7 out of 116 homozygotes developed tumo
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growth/size/body
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• around 2 - 3 months mutants develop cachexia
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• homozygotes are normal in size at birth but grow more slowly postnatally
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muscle
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• at 12 months muscular atrophy is seen
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reproductive system
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• sperm counts are about 4 time lower than in wild-type mice
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• females are infertile at least in part because of meiotic chromosome segregation defects
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• males do not sire litters probably as a result of decreased sperm counts and abnormal meiotic chromosome segregation
• sperm from males can fertilize eggs in vitro but this results in 13 times fewer 2-cell stage embryos compared to wild-type
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skeleton
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• around 2 - 3 months mutants develop lordokyphosis that increases in severity with age
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vision/eye
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• from 2 months of age, mutants develop progressive bilateral cataracts with features similar to age-related human cataracts
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homeostasis/metabolism
integument
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• at 12 months of age the subcutaneous fat cell layer is significantly thinner compared to wild-type mice
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• at 12 months of age the dermis is significantly thinner compared to wild-type mice
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bub1btm1Jvd mutation
(0 available);
any
Bub1b mutation
(58 available)
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mortality/aging
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• median lifespan of 196 days compared to 691 days in wild-type mice
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adipose tissue
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• average size of fat cells is reduced
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behavior/neurological
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• mice show reduced work output during treadmill exercise
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cardiovascular system
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• mice are highly sensitive to repeated isoproterenol administration, with half dying within 5 injections, indicating a very low cardiac stress tolerance
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cellular
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• mitotic MEFs show high rates of aneuploidy
• nearly half of MEFs exhibit whole-chromosome aneuploidy
• most aneuploidy results from chromosome gains
• aneuploidy rates in mitotic splenocytes from 5-month old mice are elevated 15%
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• MEFs exhibit impaired centrosome movement and form non-perpendicular spindles at increased rates
• MEFs show an increase in chromatin bridges
• premature chromatid separation in mitotic splenocytes from 5-month old mice is elevated
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• spindle assembly checkpoint activity is severely compromised in MEFs
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• MEFs form non-perpendicular spindles
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• marker analysis indicates an increase in senescent cells in muscles and fat tissue
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homeostasis/metabolism
muscle
skeleton
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• mice develop kyphosis with a median onset of 175 days
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vision/eye
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• mice are highly sensitive to cataract formation, with a median onset of 168 days
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bub1btm1Jvd mutation
(0 available);
any
Bub1b mutation
(58 available)
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growth/size/body
homeostasis/metabolism
liver/biliary system
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• freshly isolated primary hepatocytes show a more robust IR autophosphorylation and activating phosphorylation of AKT (pT308) in response to insulin, unlike hepatocytes from Mad2l1bptm1.1Itl/Mad2l1bptm1.1Itl Speer6-ps1Tg(Alb-cre)21Mgn/Speer6-ps1+ mice
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cellular
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• 20% (2 out of 10) live hepatocytes are aneuploid relative to none (0 of 15) wild-type hepatocytes
• aneuploidy is higher than that in hepatocytes from Mad2l1bptm1.1Itl/Mad2l1bptm1.1Itl Speer6-ps1Tg(Alb-cre)21Mgn/Speer6-ps1+ mice
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Allelic Composition |
Bub1btm1Jvd/Bub1b+
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Genetic Background |
involves: 129S6/SvEvTac |
|
Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bub1btm1Jvd mutation
(0 available);
any
Bub1b mutation
(58 available)
|
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cellular
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• after nocodazole treatment the time for 50% of cells to exit prometaphase arrest is reduced to 5.3 hours compared to 7.2 hours for wild-type MEFs
|
|
Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bub1btm1.1Jvd mutation
(0 available);
any
Bub1b mutation
(58 available)
Bub1btm1Jvd mutation
(0 available);
any
Bub1b mutation
(58 available)
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mortality/aging
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• mutants die within a few hours of birth apparently from respiratory insufficiency
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bub1btm1Jvd mutation
(0 available);
any
Bub1b mutation
(58 available)
Bub1btm2.1Jvd mutation
(0 available);
any
Bub1b mutation
(58 available)
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cellular
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• MEFs show high rates of aneuploidy and premature chromatid separation
• nearly all MEFs exhibit whole-chromosome aneuploidy
• most aneuploidy results from chromosome gains
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• MEFs show premature chromatid separation
• MEFs exhibit higher rates of chromosome missegregation and more severely compromised error correction
• MEFs exhibit impaired centrosome movement and form non-perpendicular spindles at increased rates
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• spindle assembly checkpoint activity is severely compromised in MEFs
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• MEFs form non-perpendicular spindles
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mortality/aging
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• mice die shortly after birth
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bub1btm1.1Jvd mutation
(0 available);
any
Bub1b mutation
(58 available)
Bub1btm1Jvd mutation
(0 available);
any
Bub1b mutation
(58 available)
|
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mortality/aging
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• mice fail to thrive and die within 18 hours after birth
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bub1btm1Jvd mutation
(0 available);
any
Bub1b mutation
(58 available)
Bub1btm3.1Jvd mutation
(0 available);
any
Bub1b mutation
(58 available)
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mortality/aging
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• median lifespan of 343 days compared to 691 days in wild-type mice
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growth/size/body
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• mice become growth retarded during postnatal development
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adipose tissue
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• average size of fat cells is reduced
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• fat tissue atrophy in 8-10-month old mice
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behavior/neurological
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• mice show reduced work output during treadmill exercise
|
cardiovascular system
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• mice are sensitive to repeated isoproterenol administration, with half dying within 18 injections, indicating lower cardiac stress tolerance than wild-type mice
|
cellular
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• MEFs show high rates of aneuploidy and premature chromatid separation
• nearly half of MEFs exhibit whole-chromosome aneuploidy
• most aneuploidy results from chromosome gains
• aneuploidy rates in mitotic splenocytes from 5-month old mice are elevated 38%
|
|
• MEFs exhibit impaired centrosome movement and form non-perpendicular spindles at increased rates
• premature chromatid separation in mitotic splenocytes from 5-month old mice is elevated
|
|
• spindle assembly checkpoint activity is severely compromised in MEFs
|
|
• MEFs form non-perpendicular spindles
|
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• marker analysis indicates an increase in senescent cells in muscles and fat tissue
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homeostasis/metabolism
muscle
neoplasm
N |
• mice are not prone to spontaneous tumors, with only 13% of mice dying with detectable tumors
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• incidence and multiplicity of DMBA-induced lung tumors are elevated
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• the average lung tumor size is increased in DMBA-treated mice
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skeleton
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• mice develop kyphosis with a median onset of 238 days
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vision/eye
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• mice are highly sensitive to cataract formation, with a median onset of 161 days
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|
Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bub1btm1Jvd mutation
(0 available);
any
Bub1b mutation
(58 available)
Mad2l1bptm1.1Itl mutation
(0 available);
any
Mad2l1bp mutation
(15 available)
Speer6-ps1Tg(Alb-cre)21Mgn mutation
(6 available);
any
Speer6-ps1 mutation
(4 available)
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mortality/aging
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• mice are obtained at a slightly lower than the expected number (10 versus 14.5) based on the Mendelian ratio; time of lethality is not specified
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growth/size/body
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• mice attain ~40% of normal weight at 3 weeks of age
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• mice appear normal at birth but fail to thrive, similar to Bub1btm1Jvd homozygotes
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homeostasis/metabolism
liver/biliary system
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• at 2 months of age, the cell and nuclear sizes of hepatocytes in male mice are larger than those in single knockout mice
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cellular
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• mice exhibit an increased percentage of hepatocytes with 8N or greater DNA content, indicating a striking ploidy change
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