A new genetically engineered animal model for one of the mostcommon causes of heart disease is described in today's issue ofthe journal Nature.

Experiments with transgenic mice provide the first directevidence that lipoprotein(a), a molecule that transports fat inthe bloodstream, can cause fatty deposits and hardening of thearteries that lead to heart disease and heart attacks.

Cardiovascular disease is the leading cause of death in the U.S.

Disease studies indicate one-fourth of all heart attacks arecaused by elevations in lipoprotein(a).

"Transgenic mouse technology gives you the opportunity todissect, gene by gene, the effects of different lipoproteins, theirreceptors and other likely culprits," said Richard Lawn, amolecular biologist and professor of cardiovascular medicine atStanford. "This model may be more important because it'slinked to one of the most common causes of atherosclerosis."

Lawn, a former researcher at Genentech Inc. of South SanFrancisco, Calif., pursued this research with scientists fromLawrence Berkeley Laboratory and the University of TexasSouthwestern Medical School in Dallas. They inserted thehuman gene for apolipoprotein(a), the distinguishing proteincomponent of lipoprotein(a), into a strain of mice bred forsusceptibility to atherosclerosis, and showed that 15 transgenicmice all developed fatty deposits in the arteries when fed ahigh-fat diet.

Heart disease has many causes, and its progression is notentirely understood, but it is likely that several therapies willbe applied to different types of heart disease, just as cancer istreated with a variety of methods, Stanford University MedicalCenter spokesman Don Gibbons told BioWorld.

Transgenic mice may be useful to test drugs for human disease,and the researchers are trying to breed a variety that uses thehuman "promoter" to turn on, or "transcribe" the so-called"apo(a)" gene.

"We are entering a new era," James Scott of the RoyalPostgraduate Medical School in London, wrote in an editorialaccompanying the Nature article, "in which gene promotersattached to marker genes are being screened in order todiscover compounds that interfere with gene transcription.

"This is made possible by the development of advancedrobotics and computing, and recombinant DNA methods forgenerating huge libraries of compounds. Lipoprotein(a), apo(a),the microsomal triglyceride transfer protein and their genesare prime targets for the pharmaceutical industry."

-- Nancy Garcia Senior Editor

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