Strain Name:

B6;129-Bub1bGt(neo-btk)1Dai/J

Stock Number:

010495

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Availability:

Cryopreserved - Ready for recovery

Mice heterozygous for this mutation in the budding uninhibited by benzimidazoles 1 homolog (Bub1b) gene exhibit splenomegaly, an increase in extramedullary megakaryocytes and reduced numbers of peripheral red blood cells. This mutant mouse strain may be useful in studies of early embryonic development, hematopoiesis, megakaryopoiesis, tumorigenesis and genomic instability.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6.129S4-Bub1bGt(neo-btk)1Dai/J    (Changed: 05-JUN-09 )
Type Gene Trap; Mutant Stock; Mutant Strain;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
GenerationN?F?pN1
Generation Definitions
 
Donating Investigator Wei Dai,   New York University Langone Medical Center

Description
Mice heterozygous for this mutation exhibit splenomegaly accompanied by a loss of marginal zone boundaries and an increase in mature megakaryocytes. Approximately 50% of mice have significantly reduced numbers of peripheral red blood cells, however platelet numbers are not increased. Homozygous embryos do not survive beyond early gestation (E8.5) due to impaired blastocyst proliferation and extensive apoptosis. Mouse embryonic fibroblasts from heterozygous mice exhibit defective spindle checkpoint activation, an important mechanism for genomic stability. In addition, mice are susceptible to development of lung and colon adenocarcinomas following challenge with carcinogen. Mice homozygous for the mutation are embryonic lethal. This mutant mouse strain may be useful in studies of early embryonic development, hematopoiesis, megakaryopoiesis tumorigenesis and genomic instability.

Development
A retroviral genetrap vector with a splice acceptor fused to neo with a poly A signal and a PGK promoter fused to the coding sequence of the BTK gene with a splice donor site was used to disrupt intron 1 between exon 1 and 2 of the endogenous gene. The construct was electroporated into 129-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Heterozygous offspring were crossed to C57BL/6 and then maintained by intercross.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Mosaic Variegated Aneuploidy Syndrome 1; MVA1   (BUB1B)
Premature Chromatid Separation Trait; PCS   (BUB1B)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Bub1bGt(neo-btk)1Dai/Bub1b+

        involves: 129S4/SvJae * C57BL/6
  • embryogenesis phenotype
  • *normal* embryogenesis phenotype
    • in contrast to homozygotes, heterozygous blastocysts developed normally   (MGI Ref ID J:88223)
  • hematopoietic system phenotype
  • abnormal hematopoiesis   (MGI Ref ID J:88223)
    • absent common myeloid progenitor cells
      • decreased number of erythroid progenitors   (MGI Ref ID J:88223)
      • the number of megakaryocytic progenitors was not decreased, but rather increased   (MGI Ref ID J:88223)
    • decreased erythrocyte cell number   (MGI Ref ID J:88223)
  • abnormal megakaryocyte differentiation
    • increased number of megakaryocytes   (MGI Ref ID J:88223)
    • defect in the formation of proplatelet-producing megakaryocytes   (MGI Ref ID J:88223)
    • no significant increase in the number of platelets in the peripheral blood   (MGI Ref ID J:88223)
  • enlarged spleen
    • due to increase in the number of splenic megakaryocytes   (MGI Ref ID J:88223)
  • immune system phenotype
  • enlarged spleen
    • due to increase in the number of splenic megakaryocytes   (MGI Ref ID J:88223)
  • cellular phenotype
  • abnormal megakaryocyte differentiation
    • increased number of megakaryocytes   (MGI Ref ID J:88223)
    • defect in the formation of proplatelet-producing megakaryocytes   (MGI Ref ID J:88223)
    • no significant increase in the number of platelets in the peripheral blood   (MGI Ref ID J:88223)

Bub1bGt(neo-btk)1Dai/Bub1b+

        involves: 129S4/SvJae
  • tumorigenesis
  • increased colonic adenoma incidence
    • increased incidence after administration of azoxymethane   (MGI Ref ID J:88094)
  • increased intestinal adenocarcinoma incidence
    • increased incidence after administration of azoxymethane   (MGI Ref ID J:88094)
  • cellular phenotype
  • abnormal mitotic spindle assembly checkpoint
    • in vitro studies showed impaired mitotic arrest due to defective spindle checkpoint activation   (MGI Ref ID J:88094)

Bub1bGt(neo-btk)1Dai/Bub1bGt(neo-btk)1Dai

        involves: 129S4/SvJae * C57BL/6
  • mortality/aging
  • complete embryonic lethality between somite formation and embryo turning
    • embryos die due to extensive apoptosis during early gestation, failing to survive beyond E8.5   (MGI Ref ID J:88223)
  • cellular phenotype
  • increased apoptosis
    • extensive apoptosis in embryos   (MGI Ref ID J:88223)
  • embryogenesis phenotype
  • abnormal blastocyst morphology
    • E3.5 blastocysts cultured in vitro fail to exhibit robust proliferation and become atrophic by the equivalent of E6.5   (MGI Ref ID J:88223)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Cancer Research
Increased Tumor Incidence
      Adenomas
      Adenomas: multiple tissues - induced

Developmental Biology Research
Embryonic Lethality (Homozygous)

Hematological Research
Hematopoietic Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Bub1bGt(neo-btk)1Dai
Allele Name gene trap 1, Wei Dai
Allele Type Gene trapped
Common Name(s) BUBR1-;
Mutation Made By Wei Dai,   New York University Langone Medical Center
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Gene Symbol and Name Bub1b, budding uninhibited by benzimidazoles 1 homolog, beta (S. cerevisiae)
Chromosome 2
Gene Common Name(s) AU045529; BUB1beta; BUBR1; Bub1A; MAD3L; MVA1; SSK1; expressed sequence AU045529; hBUBR1;
Molecular Note The endogenous gene was disrupted by the integration of a gene trap vector into intron 1. The gene trap vector contained a splice acceptor, neo, a polyadenylation signal, PGK-btk, and a a splice donor. [MGI Ref ID J:88223]

Genotyping

Genotyping Information


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Wang Q; Liu T; Fang Y; Xie S; Huang X; Mahmood R; Ramaswamy G; Sakamoto KM; Darzynkiewicz Z; Xu M; Dai W. 2004. BUBR1 deficiency results in abnormal megakaryopoiesis. Blood 103(4):1278-85. [PubMed: 14576056]  [MGI Ref ID J:88223]

Additional References

Bub1bGt(neo-btk)1Dai related

Dai W; Wang Q; Liu T; Swamy M; Fang Y; Xie S; Mahmood R; Yang YM; Xu M; Rao CV. 2004. Slippage of mitotic arrest and enhanced tumor development in mice with BubR1 haploinsufficiency. Cancer Res 64(2):440-5. [PubMed: 14744753]  [MGI Ref ID J:88094]

Park I; Lee HO; Choi E; Lee YK; Kwon MS; Min J; Park PG; Lee S; Kong YY; Gong G; Lee H. 2013. Loss of BubR1 acetylation causes defects in spindle assembly checkpoint signaling and promotes tumor formation. J Cell Biol 202(2):295-309. [PubMed: 23878276]  [MGI Ref ID J:201641]

Rao CV; Yang YM; Swamy MV; Liu T; Fang Y; Mahmood R; Jhanwar-Uniyal M; Dai W. 2005. Colonic tumorigenesis in BubR1+/-ApcMin/+ compound mutant mice is linked to premature separation of sister chromatids and enhanced genomic instability. Proc Natl Acad Sci U S A 102(12):4365-70. [PubMed: 15767571]  [MGI Ref ID J:97036]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation are embryonic lethal.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2085.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2710.50
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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