PUBLICATION

Zebrafish with mutations in mismatch repair genes develop neurofibromas and other tumors

Authors
Feitsma, H., Kuiper, R.V., Korving, J., Nijman, I.J., and Cuppen, E.
ID
ZDB-PUB-080707-5
Date
2008
Source
Cancer research   68(13): 5059-5066 (Journal)
Registered Authors
Cuppen, Edwin, Feitsma, Harma
Keywords
zebrafish, mismatch repair, cancer, neurofibroma, microsatellite instability
MeSH Terms
  • Abdominal Neoplasms/genetics
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Brain Neoplasms/genetics
  • DNA Mismatch Repair*
  • DNA Mutational Analysis
  • DNA Repair Enzymes/genetics*
  • DNA-Binding Proteins/genetics
  • Eye Neoplasms/genetics
  • Female
  • Hemangiosarcoma/genetics
  • Male
  • Microsatellite Instability
  • MutS Homolog 2 Protein/genetics
  • Mutation/physiology
  • Neoplasms/genetics*
  • Nerve Sheath Neoplasms/genetics
  • Neurofibromatoses/genetics*
  • Zebrafish/genetics*
PubMed
18593904 Full text @ Cancer Res.
Abstract
Defective mismatch repair (MMR) in humans causes hereditary nonpolyposis colorectal cancer. This genetic predisposition to colon cancer is linked to heterozygous familial mutations, and loss-of-heterozygosity is necessary for tumor development. In contrast, the rare cases with biallelic MMR mutations are juvenile patients with brain tumors, skin neurofibromas, and café-au-lait spots, resembling the neurofibromatosis syndrome. Many of them also display lymphomas and leukemias, which phenotypically resembles the frequent lymphoma development in mouse MMR knockouts. Here, we describe the identification and characterization of novel knockout mutants of the three major MMR genes, mlh1, msh2, and msh6, in zebrafish and show that they develop tumors at low frequencies. Predominantly, neurofibromas/malignant peripheral nerve sheath tumors were observed; however, a range of other tumor types was also observed. Our findings indicate that zebrafish mimic distinct features of the human disease and are complementary to mouse models.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes