Immunologists engineer weak-boned mice.

Researchers studying the function of an immune-system messenger called interleukin-4 (IL-4) have inadvertently created a strain of mice that develops osteoporosis. In osteoporosis, bone thins until it becomes fragile and breaks easily. These newly created mice contain a gene that causes them to make excess IL-4. "It appears that the IL-4 is somehow decreasing the production of new bone," says David B. Lewis, an immunologist at the University of Washington in Seattle.

The scientists had wanted to know how increasing the amount of this messenger in the body affects the production of immune system components called T-cells. For some reason, that genetic change also causes both male and female mice to become more and more hunchbacked during their first few months of life, says Lewis. Their bones are translucent and become progressively thinner and more oval compared to normal mice, he and his colleagues report in the Dec. 15, 1993 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES.

Typically, two kinds of cells continually remove and replace old bone. Osteoporosis can develop when bone-building cells slack off or bone-eating cells become overactive, Lewis explains. The skeletons of the mice seem to develop normally, but after birth they begin to lose bone mass.

The scientists have monitored these mice for 12 generations and know that half of each litter develops very predictable bone weakening. They hope other researchers will use the mice to study ways to rev up bone-building activity and, possibly, to develop new treatments for osteoporosis. Meanwhile, Lewis and his colleagues are looking at what happens if they block the effects of IL-4; they hope to see less bone loss.