Phenotypes Associated with This Genotype

Genotype
MGI:3046582

• Allelic Composition: Bub1b^tm1Jvd/Bub1b^tm1Jvd
• Genetic Background: involves: 129S6/SvEvTac

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

mortality/aging

premature death ( J:91128 )

• the median life span is about 6 months

adipose tissue

decreased subcutaneous adipose tissue amount ( J:91128 )

• at 12 months of age the subcutaneous fat cell layer is significantly thinner compared to wild-type mice

decreased total body fat amount ( J:91128 )

• total body fat declines prematurely

cellular

oligozoospermia ( J:91128 )

♂ • sperm counts are about 4 time lower than in wild-type mice

abnormal cell physiology ( J:91128 )

abnormal cell cycle checkpoint function ( J:105717 )

• 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

abnormal mitosis ( J:105717 )

• 17% of anaphases have multiple lagging chromosomes compared to 0% in wild-type MEFs

abnormal cellular replicative senescence ( J:91128 , J:105717 )

• 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 Rae1^tm1Jvd and Bub3^tm1Jvd (J:105717)

chromosome breakage ( J:91128 )

• 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

growth/size/body

cachexia ( J:91128 )

• around 2 - 3 months mutants develop cachexia

postnatal growth retardation ( J:91128 )

• homozygotes are normal in size at birth but grow more slowly postnatally

muscle

muscular atrophy ( J:91128 )

• at 12 months muscular atrophy is seen

reproductive system

oligozoospermia ( J:91128 )

♂ • sperm counts are about 4 time lower than in wild-type mice

female infertility ( J:91128 )

♀ • females are infertile at least in part because of meiotic chromosome segregation defects

male infertility ( J:91128 )

♂ • 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

skeleton

lordokyphosis ( J:91128 )

• around 2 - 3 months mutants develop lordokyphosis that increases in severity with age

vision/eye

cataract ( J:91128 )

• from 2 months of age, mutants develop progressive bilateral cataracts with features similar to age-related human cataracts

homeostasis/metabolism

impaired wound healing ( J:91128 )

• mutants have a decreased ability to heal wounds

integument

decreased subcutaneous adipose tissue amount ( J:91128 )

• at 12 months of age the subcutaneous fat cell layer is significantly thinner compared to wild-type mice

thin dermal layer ( J:91128 )

• at 12 months of age the dermis is significantly thinner compared to wild-type mice