Fat-free mice born Cholesterol mutants could shed light on heart disease. 19 December 2003 HELEN R. PILCHER Cholesterol is an essential part of Cell membranes and cell communication. Too much leads to cardiovascular problems. Too little is thought to be fatal. Yet the cholesterol-free animals appear to be relatively normal. "We were surprised that these mICE develop into *****hood with little effect," says Elena Feinstein of Quark Biotech, in Nes Ziona, Israel, who produced the animals1. An estimated 105 million Americans have high cholesterol. As blood levels increase, fatty deposits begin to clog up arteries. If a blockage forms, it can cause a heart attack or stroke. Exercise and healthy eating reduce cholesterol and decrease the risk of heart disease. Understanding how the molecule works may help researchers to develop new cholesterol-lowering drugs, says Feinstein. The team altered a GENE called Dhcr24, which encodes a cholesterol-making enzyme. Instead of cholesterol, the mice produced its precursor, a similar molecule called desmosterol. This hints that some cholesterol-like molecules may be interchangeable, says Feinstein. The newborn pups were 25% smaller than normal animals, and were also infertile. This shows that cholesterol is not essential for embryonic development, but is necessary for reproduction. The pups were small because they found it difficult to absorb fat from their mothers' milk. At weaning, when the animals switched to carbohydrate-rich chow, their growth caught up. The mice are now around a year old. The mutant mice that did survive may have done so by hijacking maternal cholesterol, warns cholesterol expert David FitzPatrick from the MRC Human Genetics Unit in Edinburgh, UK. Humans can't do this. Humans who carry a similar mutation are extremely rare - the two known cases died of multiple organ failure.

References Wechsler, A. et al. Generation of viable cholesterol-free mice. Science, 302, 2087, (2003). |Homepage|

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