PUBLICATION

A zebrafish bmyb mutation causes genome instability and increased cancer susceptibility

Authors
Shepard, J.L., Amatruda, J.F., Stern, H.M., Subramanian, A., Finkelstein, D., Ziai, J., Finley, K.R., Pfaff, K.L., Hersey, C., Zhou, Y., Barut, B., Freedman, M., Lee, C., Spitsbergen, J., Neuberg, D., Weber, G., Golub, T.R., Glickman, J.N., Kutok, J.L., Aster, J.C., and Zon, L.I.
ID
ZDB-PUB-050913-4
Date
2005
Source
Proceedings of the National Academy of Sciences of the United States of America   102(37): 13194-13199 (Journal)
Registered Authors
Amatruda, James F., Barut, Bruce, Hersey, Candace, Lee, Charles, Pfaff, Kathleen, Shepard, Jennifer, Spitsbergen, Jan, Stern, Howard, Zhou, Yi, Ziai, James, Zon, Leonard I.
Keywords
none
MeSH Terms
  • Genomic Instability*
  • Cyclin B/metabolism
  • Proto-Oncogene Proteins c-myb/genetics*
  • Mutation*
  • Spindle Apparatus
  • Animals
  • Genetic Predisposition to Disease
  • Mitosis
  • Zebrafish
  • Tumor Suppressor Protein p53
  • Neoplasms/etiology
  • Neoplasms/genetics*
  • Embryo, Nonmammalian
(all 13)
PubMed
16150706 Full text @ Proc. Natl. Acad. Sci. USA
Abstract
A major goal of cancer research has been to identify genes that contribute to cancer formation. The similar pathology between zebrafish and human tumors, as well as the past success of large-scale genetic screens in uncovering human disease genes, makes zebrafish an ideal system in which to find such new genes. Here, we show that a zebrafish forward genetic screen uncovered multiple cell proliferation mutants including one mutant, crash&burn (crb), that represents a loss-of-function mutation in bmyb, a transcriptional regulator and member of a putative proto-oncogene family. crb mutant embryos have defects in mitotic progression and spindle formation, and exhibit genome instability. Regulation of cyclin B levels by bmyb appears to be the mechanism of mitotic accumulation in crb. Carcinogenesis studies reveal increased cancer susceptibility in adult crb heterozygotes. Gene-expression signatures associated with loss of bmyb in zebrafish are also correlated with conserved signatures in human tumor samples, and down-regulation of the B-myb signature genes is associated with retention of p53 function. Our findings show that zebrafish screens can uncover cancer pathways, and demonstrate that loss of function of bmyb is associated with cancer.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO1-mybl2b + MO2-mybl2bstandard conditionsPrim-5
WT + MO1-mybl2b + MO2-mybl2bstandard conditionsPrim-5
WT + MO1-mybl2b + MO2-mybl2bstandard conditionsPrim-5
cdc25bcz319/cz319 (WIK)standard conditionsPrim-25
cdc25bcz319/cz319 (WIK)standard conditionsDay 4 to Day 5
dlycz3321/cz3321 (WIK)standard conditionsDay 4 to Day 5
espl1cz280/cz280 (WIK)standard conditionsPrim-25
espl1cz280/cz280 (WIK)standard conditionsDay 4 to Day 5
lamc1cz61/cz61 (WIK)standard conditionsDay 4 to Day 5
llgcz3322/cz3322 (WIK)standard conditionsDay 4 to Day 5
1 - 10 of 33
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cz61
    		Point Mutation
    cz213
      		Point Mutation
      cz226
        		Point Mutation
        cz280
          		Point Mutation
          cz319
            		Point Mutation
            cz333
              		Point Mutation
              cz3321
                		Unknown
                cz3322
                  		Point Mutation
                  1 - 8 of 8
                  Show
                  Human Disease / Model
                  No data available
                  Sequence Targeting Reagents
                  Target Reagent Reagent Type
                  mybl2bMO1-mybl2bMRPHLNO
                  mybl2bMO2-mybl2bMRPHLNO
                  1 - 2 of 2
                  Show
                  Fish
                  Fish
                  cdc25bcz319/cz319 (WIK)
                  dlycz3321/cz3321 (WIK)
                  espl1cz280/cz280 (WIK)
                  lamc1cz61/cz61 (WIK)
                  llgcz3322/cz3322 (WIK)
                  mybl2bcz226/cz226 (WIK)
                  mybl2bcz226/+ (WIK)
                  sfdcz213/cz213 (WIK)
                  slhcz333/cz333 (WIK)
                  WT
                  1 - 10 of 11
                  Show
                  Antibodies
                  No data available
                  Orthology
                  No data available
                  Engineered Foreign Genes
                  No data available
                  Mapping
                  Entity Type Entity Symbol Location
                  ESTfc17h09Chr: 11 Details
                  ESTfj39b01Chr: 11 Details
                  Featurecz226Chr: 11 Details
                  1 - 3 of 3
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                  Citation
                  Shepard, J.L., Amatruda, J.F., Stern, H.M., Subramanian, A., Finkelstein, D., Ziai, J., Finley, K.R., Pfaff, K.L., Hersey, C., Zhou, Y., Barut, B., Freedman, M., Lee, C., Spitsbergen, J., Neuberg, D., Weber, G., Golub, T.R., Glickman, J.N., Kutok, J.L., Aster, J.C., and Zon, L.I. (2005) A zebrafish bmyb mutation causes genome instability and increased cancer susceptibility. Proceedings of the National Academy of Sciences of the United States of America. 102(37):13194-13199.