Phenotypes associated with this allele

• Allele Symbol: Bub1^tm2Jvd
• Allele Name: targeted mutation 2, Jan M A van Deursen
• Allele ID: MGI:3793294
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Bub1^tm2Jvd/Bub1^tm2Jvd	involves: 129/Sv * C57BL/6	MGI:3805692
ht2	Bub1^tm2Jvd/Bub1^+	involves: 129/Sv * C57BL/6	MGI:3805690
ht3	Bub1^tm1.1Jvd/Bub1^tm2Jvd	involves: 129/Sv * C57BL/6	MGI:3805691

Genotype
MGI:3805692

hm1

• Allelic Composition: Bub1^tm2Jvd/Bub1^tm2Jvd
• Genetic Background: involves: 129/Sv * C57BL/6

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

cellular

aneuploidy ( J:135093 )

• at 5 months, metaphase spreads from splenocytes exhibit 35% incidence of aneuploidy

• aneuploid metaphases in MEFs is much higher than in Bub1^tm1.1Jvd heterozygotes or Bub1^tm2vd heterozygotes

abnormal cell cycle checkpoint function ( J:135093 )

• MEFs treated with nocadozole to induce cycle arrest are profoundly impaired in ability to maintain arrest, with 50% of cells exiting mitosis around 3.8 hours compared to arrest in prometaphase for 7.2 hours in wild-type MEFs

abnormal mitosis ( J:135093 )

• in MEFs chromosome segregation defects resulting from chromosome lagging or congression failure are observed at much higher rates than in wild-type MEFs; most events involve a single chromosome but some involve two or three chromosomes

decreased fibroblast apoptosis ( J:135093 )

• MEFs in which chromosome missegregation during mitosis occurs show a apoptotic rate of 42% compared to apoptosis of 95% of wild-type cells with such events

neoplasm

increased hepatocellular carcinoma incidence ( J:135093 )

• mice are prone to develop hepatocellular carcinomas

increased sarcoma incidence ( J:135093 )

• mice develop more sarcomas than wild-type; mice are prone to develop hepatocellular carcinomas

decreased tumor latency ( J:135093 )

• median tumor-free survival is significantly shorter than wild-type or Bub1^tm2vd homozygotes

liver/biliary system

increased hepatocellular carcinoma incidence ( J:135093 )

• mice are prone to develop hepatocellular carcinomas

Genotype
MGI:3805690

ht2

• Allelic Composition: Bub1^tm2Jvd/Bub1⁺
• Genetic Background: involves: 129/Sv * C57BL/6

cellular

aneuploidy ( J:135093 )

• at 5 months, metaphase spreads from splenocytes exhibit 6% incidence of aneuploidy

• aneuploid metaphases in MEFs is higher than in wild-type but lower than observed in Bub1^tm1.1Jvd heterozygotes or Bub1^tm2vd heterozygotes

abnormal cell cycle checkpoint function ( J:135093 )

• MEFs treated with nocadozole to induce cycle arrest are impaired in ability to maintain arrest, with 50% of cells exiting mitosis around 5.4 hours compared to arrest in prometaphase for 7.2 hours in wild-type MEFs

abnormal mitosis ( J:135093 )

• in MEFs chromosome segregation defects resulting from chromosome lagging or congression failure are observed at much higher rates than in wild-type MEFs; most events involve a single chromosome but some involve two or three chromosomes

decreased fibroblast apoptosis ( J:135093 )

• MEFs in which chromosome missegregation during mitosis occurs show a apoptotic rate of 68% compared to apoptosis of 95% of wild-type cells with such events

Genotype
MGI:3805691

ht3

• Allelic Composition: Bub1^tm1.1Jvd/Bub1^tm2Jvd
• Genetic Background: involves: 129/Sv * C57BL/6

cellular

aneuploidy ( J:135093 )

• at 5 months, metaphase spreads from splenocytes exhibit 39% incidence of aneuploidy

• aneuploid metaphases in MEFs is much higher than in Bub1^tm1.1Jvd heterozygotes or Bub1^tm2vd heterozygotes

abnormal cell cycle checkpoint function ( J:135093 )

• MEFs treated with nocadozole to induce cycle arrest are impaired in ability to maintain arrest, with 50% of cells exiting mitosis around 3.5 hours compared to arrest in prometaphase for 7.2 hours in wild-type MEFs

abnormal mitosis ( J:135093 )

• 15% of mitotic figures from splenocytes show premature separation of sister chromatids

• in MEFs chromosome segregation defects resulting from chromosome lagging or congression failure are observed at much higher rates than in wild-type MEFs; most events involve a single chromosome but some involve two or three chromosomes

decreased fibroblast apoptosis ( J:135093 )

• MEFs in which chromosome missegregation during mitosis occurs show a apoptotic rate of 32% compared to apoptosis of 95% of wild-type cells with such events

neoplasm

increased lymphoma incidence ( J:135093 )

• mice develop more lymphomas than wild-type

increased sarcoma incidence ( J:135093 )

• mice develop more sarcomas than wild-type

increased lung tumor incidence ( J:135093 )

• mice develop more lung tumors than wild-type

decreased tumor latency ( J:135093 )

• median tumor-free survival is significantly shorter than wild-type or Bub1^tm2vd homozygotes

respiratory system

increased lung tumor incidence ( J:135093 )

• mice develop more lung tumors than wild-type