Phenotypes associated with this allele

• Allele Symbol: Bub1b^tm3.1Jvd
• Allele Name: targeted mutation 3.1, Jan M A van Deursen
• Allele ID: MGI:6478925
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Bub1b^tm3.1Jvd/Bub1b^+	involves: 129S6/SvEvTac * C57BL/6	MGI:6478928
ht2	Bub1b^tm2.1Jvd/Bub1b^tm3.1Jvd	involves: 129S6/SvEvTac * C57BL/6	MGI:6478926
ht3	Bub1b^tm1Jvd/Bub1b^tm3.1Jvd	involves: 129S6/SvEvTac * C57BL/6	MGI:6478931

Genotype
MGI:6478928

ht1

• Allelic Composition: Bub1b^tm3.1Jvd/Bub1b⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

cellular

abnormal chromosome number ( J:293084 )

• 28% of mitotic splenocytes show abnormal chromosome numbers

aneuploidy ( J:293084 )

• MEFs show an elevation in aneuploidy

• aneuploidy is increased in livers and lungs, but not spleen

abnormal mitosis ( J:293084 )

• MEFs and mitotic splenocytes exhibit premature chromatid separation

• MEFs exhibit small, but significant, increase in chromosome segregation errors; both spindle assembly checkpoint and attachment error correction machinery are impaired

• MEFs exhibit increased chromosome lagging, forming non-perpendicular spindles and elevated rates due to slow centrosome movement

abnormal mitotic spindle assembly checkpoint ( J:293084 )

• spindle assembly checkpoint is impaired in MEFs

abnormal mitotic spindle morphology ( J:293084 )

• MEFs form non-perpendicular spindles

neoplasm

neoplasm ( J:293084 )

N • incidence and spectrum of spontaneous tumors are similar to wild-type

increased tumor growth/size ( J:293084 )

• DMBA-treated mice show no increase in lung tumor incidence, however, lung tumor size is increased

decreased tumor latency ( J:293084 )

• although incidence and spectrum of spontaneous tumors are similar to wild-type, tumor latencies are reduced (770 days versus 886 days in wild-type mice)

• lymphomas which develop with reduced latencies contain more mitotic cells than lymphomas from wild-type mice

mortality/aging

mortality/aging ( J:293084 )

N • mice show a strong trend toward reduced median lifespan that is close to reaching significance

N • mice show no evidence of accelerated aging phenotypes

Genotype
MGI:6478926

ht2

• Allelic Composition: Bub1b^tm2.1Jvd/Bub1b^tm3.1Jvd
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

mortality/aging

embryonic lethality prior to tooth bud stage ( J:293084 )

• no newborn pups are detected; embryos are seen at E3.5 but not at E13.5

• attempts to culture the inner cell mass from blastocysts are unsuccessful, indicating that early embryonic death is due to mitotic failure

Genotype
MGI:6478931

ht3

• Allelic Composition: Bub1b^tm1Jvd/Bub1b^tm3.1Jvd
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

mortality/aging

premature death ( J:293084 )

• median lifespan of 343 days compared to 691 days in wild-type mice

premature aging ( J:293084 )

growth/size/body

postnatal growth retardation ( J:293084 )

• mice become growth retarded during postnatal development

adipose tissue

decreased fat cell size ( J:293084 )

• average size of fat cells is reduced

lipodystrophy ( J:293084 )

• fat tissue atrophy in 8-10-month old mice

behavior/neurological

decreased grip strength ( J:293084 )

impaired exercise endurance ( J:293084 )

• mice show reduced work output during treadmill exercise

cardiovascular system

increased response of heart to induced stress ( J:293084 )

• mice are sensitive to repeated isoproterenol administration, with half dying within 18 injections, indicating lower cardiac stress tolerance than wild-type mice

cellular

aneuploidy ( J:293084 )

• 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%

abnormal mitosis ( J:293084 )

• 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

abnormal mitotic spindle assembly checkpoint ( J:293084 )

• spindle assembly checkpoint activity is severely compromised in MEFs

abnormal mitotic spindle morphology ( J:293084 )

• MEFs form non-perpendicular spindles

early cellular replicative senescence ( J:293084 )

• marker analysis indicates an increase in senescent cells in muscles and fat tissue

homeostasis/metabolism

impaired exercise endurance ( J:293084 )

• mice show reduced work output during treadmill exercise

increased response of heart to induced stress ( J:293084 )

• mice are sensitive to repeated isoproterenol administration, with half dying within 18 injections, indicating lower cardiac stress tolerance than wild-type mice

increased incidence of tumors by chemical induction ( J:293084 )

• incidence and multiplicity of DMBA-induced lung tumors are elevated

muscle

skeletal muscle fiber atrophy ( J:293084 )

neoplasm

neoplasm ( J:293084 )

N • mice are not prone to spontaneous tumors, with only 13% of mice dying with detectable tumors

increased incidence of tumors by chemical induction ( J:293084 )

• incidence and multiplicity of DMBA-induced lung tumors are elevated

increased tumor growth/size ( J:293084 )

• the average lung tumor size is increased in DMBA-treated mice

skeleton

kyphosis ( J:293084 )

• mice develop kyphosis with a median onset of 238 days

vision/eye

cataract ( J:293084 )

• mice are highly sensitive to cataract formation, with a median onset of 161 days

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mosaic variegated aneuploidy syndrome 1		DOID:0080141	OMIM:257300	J:293084