New Technique Aids Search for Tumor Suppressor Genes

HHMI researchers at Baylor College of Medicine have developed a genetic engineering technique to create mice missing large segments of individual chromosomes. Such animals could provide an excellent tool for finding tumor suppressor genes and studying the effects of large-scale gene deletions.

Tumor suppressor genes produce proteins that can halt the cell growth cycle. When these genes do not function, cancer may result. Gene failure may stem from direct mutation or gene deletion, in which the part of the chromosome containing the gene is lost.

As a result of these errors, people who develop cancer may inherit only one functional copy of a tumor suppressor gene. The stage may be set for the development of sporadic breast cancer, for example, when a woman loses her only remaining copy of a tumor suppressor gene.

Reporting in Nature last year, Allan Bradley, an HHMI investigator at Baylor, with associates Ramiro Ramírez-Solis, now of Texas A&M; University and Pentao Liu, also of HHMI at Baylor, used an enzyme called "Cre" (pronounced kree) to cut and rejoin large segments of DNA in mouse chromosomes in embryonic stem cells. The cells with missing genetic information were then used to produce mice with the chromosome changes.

With this technology, scientists may be able to study mice with cancer or other disorders caused by chromosomal changes affecting large DNA segments during development. Once the chromosome-deficient mice are bred, the next step is to note the consequences of gene deletion. Eventually, researchers hope to identify and clone the genes involved.