Lack of skeletal muscle transcription factor MondoA turns mice into mini-Usain Bolts
When mice lack MondoA, a transcription factor that mediates response to glucose, they become the “Usain Bolts” of the mouse world, sprinting faster than their normal counterparts, said researchers from Baylor College of Medicine in a report that appears online in the Biochemical Journal.
“When we knocked this factor out, we saw very little in terms of phenotype (outward signs),” said Dr. Lawrence Chan, professor and section chief of medicine – endocrinology, diabetes and metabolism and director of the Diabetes Research Center at Baylor. “They look healthy, eat normally and have no major problem we can see with glucose regulation. They do not have diabetes.”
However, when they examined the pathways involved in glycolysis (the process of breaking down glucose and enabling the release of energy) in these animals, they found that the mice had enhanced glycolytic capacity.
“They can supply energy in a hurry but not in a sustained fashion,” said Chan. While the mice are set up to be sprinters, they are not designed to be marathoners.
To test their hypothesis, Chan and his colleagues put the mice on treadmills. As they gradually increased the speed of the treadmills, it became obvious that the mice that lacked MondoA ran faster than the normal (or wild-type) mice that had the transcription factor.
However, the mice without MondoA could not sustain the faster speed.
“If we have them run longer at a moderate speed, they do no better than mice who have MondoA,” said Chan.
“This helps us understand more about the physiology of sprinting,” said Chan. While the finding might tempt those who want to cheat in sports, that is not the motivation of the scientists involved in this research.
“Sprinting has some protective value,” Chan pointed out. “When you see a lion coming at you, you had better sprint.”
Others who took part in this work include Minako Imamura, Benny Chang, Motoyuki Kohjima and Ming Li of Baylor, Byounghoon Hwang, and Robert Harris of the Richard Roudebush VA Medical Center in Indianapolis, and Heinrich Taegtmeyer of The University of Texas Health Science Center at Houston.
Funding for this work came from the National Institutes of Health (Grants R01HL058586, R01DK084496 and P30DK079638 [for the Diabetes Research Center], R01HL061483, a Veterans Affairs Merit Review Award and the Betty Rutherford Chair for Diabetes Research.
Chan holds the Betty Rutherford Chair for Diabetes Research.