Drs. Ming-Jer and Sophia Tsai, professors of molecular and cellular biology at BCM, have studied COUP-TFII (Chicken Ovalbumin Upstream Promoter Transcription Factor II) for decades, but only when they bred mice that had only one gene copy for the factor did they find that the animals had smaller fat cells and increased energy metabolism as well as enhanced response to insulin.

"If a mouse loses one copy of the gene, the animal becomes lean," said Ming-Jer Tsai. "It is more sensitive to the effects of insulin and resistant to obesity from a high fat diet."

Their studies raise the likely possibility that one can use COUP-TFII as a potential drug target for diabetes and obesity treatment.

Identifying a drug that could reduce the effect of COUP-TFII activity has become a future focus for their research, said Sophia Tsai.

"We don't need to inhibit it totally," she said. "Partial inhibition will do the trick as when you lose one copy of the gene, your fat cells are already much smaller and the animal is lean."

The animals not only have less fat, they also have more muscle and burn more energy, said Ming-Jer Tsai.

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Mutation of RANBP2 is not the only susceptibility gene for the disease, although researchers said it accounted for 75 percent of the cases of familial or recurrent cases in the current study, showing up in 12 of 16 families. The gene mutation in itself is insufficient to cause full-blown ANE1. Additional genetic and environmental factors - such as the specific biological route the virus takes and a person's nutritional status - may also be important considerations, the researchers said.

The study included nearly two hundred children and adults from 35 unrelated families, 50 of whom had confirmed episodes of ANE. Nineteen patients of European, Asian or African descent had isolated cases of ANE. None of the participants with isolated ANE, as well as over a thousand healthy control patients, carried the RANBP2 mutation. The rest of the participants came from 16 families of European descent affected by familial or recurrent forms of the disease.

In one family central to the current study, 16 family members had clinical symptoms of ANE. Presence of the disease was confirmed through pathologic examination of two children who died from their illness. About half of the family members also carried the gene mutation. Of those, slightly less than half had a previous episode of ANE, and about half of the individuals who became ill had recurrent ANE, the researchers said.

ANE was initially found in Asia and is now known to affect children worldwide. Cases in the United States are thought to be under-reported, Dr. Neilson said. The disease is known for causing neurologic injury in children following common infections, like flu. According to the U.S. Centers for Disease Control, the disease includes lesions of the brain and brain stem. The disease progresses rapidly with symptoms that include cough, vomiting and diarrhea in combination with neurologic dysfunction, alteration of consciousness and seizures. The disease is often fatal, or it can lead to long-term health problems for surviving patients.

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