THURSDAY, Dec. 18, 2003 (HealthDayNews) -- Mice that have no cholesterol have been bred, and while the feat does not have immediate clinical importance, scientists hope it will further the understanding of what role cholesterol plays in humans.
"Cholesterol is an important sterol in all mammals," says lead researcher Elena Feinstein of Quark Biotech Inc. "It is an indispensable structural block in cells and their membranes and plays a major role in many body functions."
Feinstein's group developed mice with a genetic mutation that caused cholesterol to be replaced by another sterol, desmosterol, a sterol found in some shellfish. These cholesterol-free mice are smaller than normal mice and are also infertile but otherwise relatively healthy, according to the report, which appears in the Dec. 19 issue of Science.
Theses genetically altered mice are infertile because cholesterol is needed in the production of sex hormones.
It was possible to develop these mice because during gestation mice get their cholesterol from their mother, unlike humans, where the fetus must rely on its own production of cholesterol, Feinstein says.
She adds there are two known cases of humans born without cholesterol. Of these, one was born dead and the other is still alive but malformed.
In humans, cholesterol is essential for development, but in adult life it seems largely interchangeable with desmosterol, Feinstein says.
"It was a great surprise that mice that lacked cholesterol were viable with minimal malformation," Feinstein says. "These mice are useful in research, allowing us to understand which organs and systems are dependent on cholesterol and which are not."
This finding may also aid in the understanding of how to block cholesterol, Feinstein says.
"There are a lot of organisms that exist that don't make cholesterol," says Dr. Robert F. Zelis, a professor of medicine at Pennsylvania State University. "However, one of the things that we use cholesterol for is to hold cell membranes together."
"That they got mice to live with desmosterol is interesting, but not out of the realm of possibility," he adds. "It is interesting that you don't need cholesterol to maintain cellular membrane structure, but can substitute something else."
In the early 1960s a drug called triparanol, which blocked cholesterol in the same way that cholesterol was blocked in the mice, produced a lot of desmosterol, which led to the development of cataracts, Zelis says.
Feinstein says triparanol did not completely block the enzyme she targeted to make her mice cholesterol-free and, despite the production of desmosterol, she has not seen cataracts in the altered mice.
It is possible this discovery may lead to new cholesterol-lowering drugs that eliminate some of the side effects of statins, but what other consequences it might have are unknown, Zelis says.
More information
To learn more about cholesterol, visit the American Heart Association or the National Heart, Lung, and Blood Institute.
