Researchers have created a strain of viable cholesterol-free mice, which may help shed light on the molecule's biological roles in humans. Although excess cholesterol is associated with health problems including heart attacks and strokes, the fatlike molecule has a number of important functions: it is a cell membrane component and a precursor to sex steroids and a number of other signaling molecules.

Elena Feinstein of Quark Biotech (Cleveland, OH) and her colleagues knocked out the gene Dhcr24, which encodes for an enzyme that converts a cholesterol precursor, desmosterol, to cholesterol. Dhcr24−/− pups were 25% smaller than their Dhcr24+/+ and Dhcr24+/− littermates and were infertile (Science, 19 December 2003). The double knockouts, which have survived to adulthood, accounted for 10–17% of pups born from Dhcr24+/− matings, rather than the expected 25%, suggesting a degree of embryonic lethality.

This phenotype is mild compared with that seen in humans with the extremely rare condition desmosterolosis, which results from mutations in the DHCR24 gene. A possible explanation for this discrepancy is that developing mice can absorb cholesterol from their mothers, while human embryos cannot. These results also suggest that, at least in mice, desmosterol is able to replace cholesterol in a number of functions.