‘Sleep Gene’ Identified: FABP7

An international team of scientists from the United States and Japan has seen how a particular gene, called the fatty acid binding protein 7 (FABP7), is involved in the quality of sleep experienced by three different animals, including humans. The study was published in the April 5, 2017 issue of the journal Science Advances.

Gerstner et al found that a mutation in the gene FABP7 is associated with fragmented sleep in humans. Image credit: Wok  Apix.

Gerstner et al found that a mutation in the gene FABP7 is associated with fragmented sleep in humans. Image credit: Wok Apix.

“Sleep must be serving some important function. But as scientists we still don’t understand what that is. One way to get closer to that is by understanding how it is regulated or what processes exist that are shared across species,” said lead author Dr. Jason Gerstner, from the Elson S. Floyd College of Medicine at Washington State University.

Dr. Gerstner and co-authors looked at genes that change expression over the sleep-wake cycle and found expression of the gene FABP7 changed over the day throughout the brain of mice.

They saw that mice with a knocked out FABP7 gene slept more fitfully compared to normal mice with the gene intact.

This suggested FABP7 is required for normal sleep in mammals.

To see if FABP7 is indeed required for normal sleep in humans, the researchers looked at data from nearly 300 Japanese men who underwent a seven-day sleep study that included an analysis of their DNA.

It turned out that 29 of them had a variant of the gene responsible for the production of the FABP7 protein. Like the mice, they tended to sleep more fitfully.

While they would get the same amount of sleep as other people, their sleep was not as good, with more waking events when they should be sleeping.

Finally, the authors made transgenic fruit flies. They inserted mutated and normal human FABP7 genes into star-shaped glial cells called astrocytes.

Glial cells were long thought to be mere supporting characters to neurons, the processors of information in the brain. But researchers more recently have found that, like neurons, glial cells release chemical neurotransmitters and control behavior.

To monitor the flies’ sleep, the team used the ‘Drosophila Activity Monitor’ that automatically records activity changes using an infrared beam to determine if a fly is awake or asleep. If the beam is unbroken for five or more minutes, the machine concludes the fly is asleep.

It turned out that flies with the mutated FABP7 gene broke the beam more frequently during the normal sleep time.

Like mice and humans without a properly functioning FABP7 gene, mutant FABP7 flies slept more fitfully.

“This suggests that there’s some underlying mechanism in astrocytes throughout all these species that regulates consolidated sleep,” Dr. Gerstner said.

“Moreover, it’s the first time we’ve really gained insight into a particular cell’s and molecular pathway’s role in complex behavior across such diverse species.”

Even more remarkable is that fruit flies have been on the planet for some 60 million years.

“That suggests we have found an ancient mechanism that persisted over evolutionary time. Evolution does not keep something around that long if it is not important,” Dr. Gerstner said.

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Jason R. Gerstner et al. 2017. Normal sleep requires the astrocyte brain-type fatty acid binding protein FABP7. Science Advances 3 (4): e1602663; doi: 10.1126/sciadv.1602663

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