Phenotypes associated with this allele

• Allele Symbol: Bub1b^tm2.1Jvd
• Allele Name: targeted mutation 2.1, Jan M A van Deursen
• Allele ID: MGI:5487826
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Bub1b^tm2.1Jvd/Bub1b^+	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:5487831
ht2	Bub1b^tm2.1Jvd/Bub1b^+	involves: 129S6/SvEvTac * C57BL/6	MGI:6478929
ht3	Bub1b^tm2.1Jvd/Bub1b^tm3.1Jvd	involves: 129S6/SvEvTac * C57BL/6	MGI:6478926
ht4	Bub1b^tm1Jvd/Bub1b^tm2.1Jvd	involves: 129S6/SvEvTac * C57BL/6	MGI:6478932

Genotype
MGI:5487831

ht1

• Allelic Composition: Bub1b^tm2.1Jvd/Bub1b⁺
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6

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

Accelerated cataract formation in Bub1b^tm2.1Jvd/Bub1b⁺ mice

mortality/aging

premature death ( J:194926 )

• reduced median (93 vs. 102 weeks) and maximum lifespan

premature aging ( J:194926 )

• accelerated onset of age-related phenotypes

adipose tissue

decreased subcutaneous adipose tissue amount ( J:194926 )

• at 104 weeks without a decrease in the dermal layer thickness

decreased total body fat amount ( J:194926 )

• reduced total fat mass at 24 months

• reduced fat depot size at 104 weeks

decreased fat cell size ( J:194926 )

• at 104 weeks

abnormal fat pad morphology ( J:194926 )

• reduced subscapular fat pad weight at 24, but not 15, months

decreased inguinal fat pad weight ( J:194926 )

• at 24, but not 15, months

decreased mesenteric fat pad weight ( J:194926 )

• at 24, but not 15, months

cellular

aneuploidy ( J:194926 )

• in mouse embryonic fibroblasts

abnormal mitosis ( J:194926 )

• incidence of premature chromosome separation in mouse embryonic fibroblasts is increased compared to in wild-type

early cellular replicative senescence ( J:194926 )

• age-related

skeleton

skeleton phenotype ( J:194926 )

N • mice exhibit normal bone mineral density

lordokyphosis ( J:194926 )

• lordokyphosis at 89 weeks without evidence of osteoporosis

muscle

decreased skeletal muscle fiber diameter ( J:194926 )

• at 15 months in the gastrocnemius, paraspinal and abdominal muscles

• however, muscle fiber diameter at 3 months

muscular atrophy ( J:194926 )

• pronounced by 65 weeks

neoplasm

neoplasm ( J:194926 )

N • spontaneous tumor incidences are normal

increased tumor growth/size ( J:194926 )

• mice treated with DMBA exhibit larger lung tumor size compared with wild-type mice

• however, tumor incidence and multiplicity are normal

homeostasis/metabolism

impaired exercise endurance ( J:194926 )

• reduced at 65 weeks

growth/size/body

decreased body weight ( J:194926 )

• at 24, but not 15, months

cardiovascular system

cardiovascular system phenotype ( J:194926 )

N • unlike Bub1b^tm1Jvd homozygotes, mice do not exhibit cardiac arrhythmias

integument

decreased subcutaneous adipose tissue amount ( J:194926 )

• at 104 weeks without a decrease in the dermal layer thickness

vision/eye

cataract ( J:194926 )

• at 101 weeks

behavior/neurological

impaired exercise endurance ( J:194926 )

• reduced at 65 weeks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mosaic variegated aneuploidy syndrome 1		DOID:0080141	OMIM:257300	J:194926

Genotype
MGI:6478929

ht2

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

cellular

abnormal chromosome number ( J:293084 )

• 18% of mitotic splenocytes show abnormal chromosome numbers

aneuploidy ( J:293084 )

• mouse embryo fibroblasts (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

Genotype
MGI:6478926

ht3

• 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:6478932

ht4

• Allelic Composition: Bub1b^tm1Jvd/Bub1b^tm2.1Jvd
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

cellular

aneuploidy ( J:293084 )

• MEFs show high rates of aneuploidy and premature chromatid separation

• nearly all MEFs exhibit whole-chromosome aneuploidy

• most aneuploidy results from chromosome gains

abnormal mitosis ( J:293084 )

• 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

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

mortality/aging

neonatal lethality, complete penetrance ( J:293084 )

• mice die shortly after birth