World Health Matters: Belgium: GM mice cast doubt on diabetes research

by Gary Finnegan: Could years of diabetes research have been in vain? That is the question occupying scientists after the publication of a new study by researchers in KU Leuven which questions the value of using a special breed of mice in preclinical studies.

The mice had their DNA altered with a human growth hormone gene. However, it now appears that the gene had an unintended effect on the mice’s insulin production, a key variable in diabetes research.

The use of genetically modified mice has been standard practice in medical research for over thirty years. To expedite the cutting-and-pasting of fragments of DNA, the pioneers of the method inserted a human growth hormone gene alongside other modified DNA.

Researchers assumed that the DNA of the human growth hormone would remain tightly encapsulated in the modified DNA of the mouse. They did not expect the mice to begin producing their own human growth hormone – but that appears to be exactly what happened.

KU Leuven professors Frans Schuit and John Creemers used the genetically modified mice regularly in their lab. To their surprise, they observed that the mice showed pregnancy-like symptoms despite not being pregnant.

Digging deeper, the researchers discovered that this pregnancy-like state was being caused by the human growth hormone, according to Professor Schuit.

Roughly 250 published studies about diabetes were conducted using these tainted mice, says Professor Creemers. “In many of them, researchers were looking to see if a given gene played a role in insulin production. The genetically modified mice distort the results because of the human growth hormone, so in many cases the effect of that gene was either overvalued or undervalued. Those results now need to be reinterpreted,” he said.

He added that there are genetically modified mice available today that do not include human growth hormone. “These mice can be used to reinterpret previous results,” Professor Creemers said.

Professor Schuit noted that stepping back and correcting false assumptions is part and parcel of the scientific method. “We have to continue verifying our methods with a critical eye, even if it means that research advances at a slower pace. For diabetes research, this unexpected turn is an important step forward. Now that the haze around the artificial growth hormone has been cleared, scientists can plan future research with a clear vision.”