Superheroes are a pop culture phenomenon. Their amazing abilities entertain and inspire us, but hardly seem attainable in the real world. However, superpowers may be closer to reality than you think. Real-life super-mice are thriving in labs all over the world. These gifted little rodents aren’t exactly preparing to defend the earth from supervillains or alien invaders, but they are powerful examples of the potential for biomedical research.
By overexpressing phosphoenolpyruvate carboxykinase (GTP) (PEPCK-C) in skeletal muscle, researchers at Case Western Reserve University have made mice with incredible energy metabolism1. These mice are faster than control mice, are capable of running for several hours without resting (approximately 30 times as long as control mice), have low body fat, and have more mitochondria and triglycerides in their muscles. Shockingly, these mice live longer than wild-type mice and maintain their super abilities well into old age. Mice with similar abilities were generated by another group through muscle-specific inactivation of the nuclear receptor corepressor 1 (NCoR1) gene2. Applications of these results may eventually be used to treat muscle and metabolic pathologies.
In general, mammals lack the ability to regrow lost tissues. However, the Murphy Roths Large (MRL) mouse strain shows remarkable regenerative abilities, including rapid and scarless healing of ear-punch wounds, amputated digit tips, peripheral nerve and cornea damage, and even cardiac wounds3. These mice carry dozens of mutations which may contribute to their super-healing abilities, but there is strong evidence that p21 plays a significant role4. Knowledge from studies of these mice may one day allow humans to regrow lost limbs and perfectly heal from serious injuries
Neuroscientists at Florida State University have improved the already amazing murine nose by knocking out the Kv1.3 potassium channel5. These mice have a sense of smell that is between 1,000 and 10,000 times more sensitive than wild-type mice, and also have improved odor discrimination. Studies of these mice have improved our understanding of olfactory function, and may contribute to treatments for people with anosmia.
Researchers at the University of Rochester Medical Center have generated chimeric mice containing human glial cells in their brains, which makes them faster learners in many different behavioral tests6. These mice should provide valuable information about the role of accessory cells in the brain, and about interspecies differences in CNS function.
Another type of genius mice were made by replacing the mouse Foxp2 transcription factor with a human form of the gene7. These humanized knockin mice can more quickly switch between declarative and procedural learning, and can easily master mazes that require both types of learning, likely due to differences in dopamine signaling and synaptic plasticity. Studies with these mice should help us better understand different types of learning, and should help elucidate the function of Foxp2, which is known to play a key role in human learning and language.
What superpowers do you want to try?
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- Hakimi P et al. (2007) Overexpression of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) in skeletal muscle repatterns energy metabolism in the mouse. J. Biol. Chem. 282:32844-55
- Yamamoto H et al. (2011) NCoR1 is a conserved physiological modulator of muscle mass and oxidative function. Cell 147:827-39
- Raia MF and Sandell LJ. (2014) Regeneration of articular cartilage in healer and non-healer mice. Matrix Biology 39:50-5
- Heber-Katz E, Zhang Y, Bedelbaeva K, Song F, Chen X, Stocum DL (2013) Cell cycle regulation and regeneration. Curr Top Microbiol Immunol. 367:253-76
- Fadool DA et al. (2004) Kv1.3 channel gene-targeted deletion produces "Super-Smeller Mice" with altered glomeruli, interacting scaffolding proteins, and biophysics. Neuron 41:389-404
- Han X et al. (2013) Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice. Cell Stem Cell 12:342-53
- Schreiweis C et al. (2014) Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance. PNAS 111:14253-8