Gene affecting bone mass identified as potential human therapeutic target.

2004 FEB 5 - (NewsRx.com & NewsRx.net) -- Researchers at Oregon Health & Science University (OHSU), Portland Veterans Affairs Medical Center (VAMC), and Roche have identified a gene affecting skeletal development in mice that may have relevance to human osteoporosis.

The study, titled "Regulation of bone mass in mice by the lipoxygenase gene Alox 15," was published in the January 9, 2004, edition of Science.

The gene, Alox15, was isolated from a region of a chromosome known to strongly influence peak bone mineral density (BMD) in mice, according to a study led by the OHSU Bone and Mineral Research Unit and VAMC. Low bone mineral density in early adulthood is considered a major risk factor for osteoporosis in humans.

Robert F. Klein, MD, OHSU associate professor of medicine and the study's lead author, said Alox15 was uncovered through analysis of a mouse genetic model of osteoporosis.

"Between 60% and 80% of natural variations in bone density is genetically determined, and understanding this gene's importance in normal skeletal physiology is a goal of bone and mineral research," he said. "This is a major step forward."

Gary Peltz, MD, PhD, head of genetics at Roche Palo Alto and a study co-author, said: "The study demonstrates that mouse genetic discoveries can lead to new opportunities for human therapeutics. It also demonstrates how the rate of genetic discovery was accelerated by coupling genetic analysis of an experimental murine disease model with gene expression analysis."

Alox15 encodes an enzyme called 12/15-lipoxygenase that converts fatty acids into binding molecules, or ligands, for the peroxisome proliferator-activated receptor-gamma (PPARg). The PPARg receptor is present in many cell types, including pluripotent marrow stem cells that can ultimately develop into either adipocytes (fat cells) or osteoblasts (bone-forming cells).