Developing Genetically Engineered Mouse Models to Study Tumor Suppression

Shunbin Xiong1, Jan Parker‐Thornburg2, Guillermina Lozano1

1 Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas, 2 Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Houston, Texas
Publication Name:  Current Protocols in Mouse Biology
Unit Number:   
DOI:  10.1002/9780470942390.mo110159
Online Posting Date:  March, 2012
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Since the late 1980s, the tools to generate mice with deletions of tumor suppressors have made it possible to study such deletions in the context of a whole animal. Deletion of some tumor suppressors results in viable mice while deletion of others yield embryo lethal phenotypes, cementing the concept that genes that often go awry in cancer are also of developmental importance. More sophisticated mouse models were subsequently developed to delete a gene in a specific cell type at a specific time point. Additionally, incorporation of point mutations in a specific gene as observed in human tumors has also revealed their contributions to tumorigenesis. On the other hand, some models never develop cancer unless combined with other deletions, suggesting a modifying role in tumorigenesis. This review will describe the technical aspects of generating these mice and provide examples of the outcomes obtained from alterations of different tumor suppressors. Curr. Protoc. Mouse Biol. 2:9‐24 © 2012 by John Wiley & Sons, Inc.

Keywords: knockout; knock‐in; translocation; transgenic mouse; phenotype analysis

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Table of Contents

  • Introduction
  • Gene Deletion via Knockout Targeting Strategies
  • Characterizing Tumor Models
  • Generation of Mice with Deletions of Tumor Suppressors
  • Generating Conditional Loss‐of‐Function Alleles
  • Conditional Loss‐of‐Function Alleles for Tumor Suppressors Bypass Lethality and Expand Tumor Phenotypes
  • Generating Knock‐In Alleles
  • Translocations
  • Transgenic Mice
  • Allele Preservation
  • Literature Cited
  • Figures
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Literature Cited

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