Runx3 knockouts and stomach cancer.
Gene targeting often results in knockout mice that show several phenotypes, some of which may not directly relate to the intrinsic function of the disrupted gene. Hence, to study the biological function of genes using knockout mice, one must identify the defects that are directly due to the loss of the targeted gene. Runx3 is a transcription factor that regulates lineage-specific gene expression in developmental processes. Recently, two groups produced Runx3 knockout mice. Two comparable defects were identified in both knockout strains, one involved neurogenesis and the other thymopoiesis. In addition, a stomach defect pertaining to gastric cancer was observed in one of the mutant strains, but not in the other. Here, we assess the differences between the two Runx3 mutant strains and discuss further studies that could reconcile these discrepancies. This article highlights the difficulties of inferring gene function through the interpretation of knockout phenotypes.
Levanon
Ditsa
D
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
Brenner
Ori
O
Otto
Florian
F
Groner
Yoram
Y
D000818:Animals; D019070:Cell Lineage; D050677:Core Binding Factor Alpha 3 Subunit; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D013274:Stomach Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; C493729:Runx3 protein, human; C493730:Runx3 protein, mouse; D014157:Transcription Factors