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Inside Tract - Take (vitamin D) and see

Inside Tract Spring 2011

Take (vitamin D) and see

Date: April 1, 2011

It’s a good example of serendipity—the events in Xuhang Li’s lab that pulled vitamin D into focus.
It’s a good example of serendipity—the events in Xuhang Li’s lab that pulled vitamin D into focus.

An odd thing happened in Xuhang Li’s lab as he researched a more realistic animal model of ulcerative colitis—something that sprang unexpectedly from due diligence and mouse chow. Now there may be another feather in vitamin D’s cap.

Here’s the story: Li, a molecular biologist/biochemist, has been investigating the biology behind the diarrhea that marks the larger category of inflammatory bowel disease (IBD). “So far, the particulars of that have escaped us,” he says.

Yet earlier, Li had found one particular: In tests of standard animal models of IBD and in patients with active disease, there’s a consistent drop in a protein called Clc-5. It’s a chloride ion channel—a reasonable culprit when osmosis has gone astray. But Li thought there might be more to the molecule.

A body of work suggests that IBD’s diarrhea somehow involves a rise in specific cytokines, the immune agents of inflammation. Could Clc-5 play a part? Genetically knocking out the protein in mice, Li reasoned, might show if it somehow sparks immune effects. It could also make a model that mirrors the human disease more closely.

So his lab tested mice engineered to lack Clc-5 genes. (As a prudent backup, another supply of engineered mice were kept off-site at a commercial facility.) The animals grew normally with no overt intestinal problems. Compared with controls, however, their level of IL-6, a cytokine closely linked to IBD, was unusually high.

As a next step, both test and control mice were treated chemically to induce colitis and again compared. Results were clear: The Clc-5 knockout mice were far more susceptible to colitis, suggesting that, in mice as in humans, having less Clc-5 protein ups the possibility of symptoms.

But it was when Li’s lab went to repeat the studies with a larger number of mice that they found the unexpected.

The team went to fetch more mice, but on-site supplies were short. No problem. The facility delivered more and, as before, colitis was induced. “But now we had trouble,” says Li. “One afternoon my postdoc came in, shaking her head: This experiment doesn’t work. These mice resist the induced colitis.”

Li suggested a second try; results were the same. What could it be? After narrowing the possibilities, Li realized it was the chow. The shipped-in mice had a diet higher in vitamin D.

Soon, a side experiment showed the vitamins’ benefit to colitis-prone animals was no fluke. “We know that patients with IBD are greatly affected by what they eat,” says Li, who’s begun an extensive literature search.

“Our work and others’ suggests that Vitamin D plays an important immunosuppressive role,” he explains, “and we need to look into it.

“Now our whole lab takes vitamin D.”

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