Rare regeneration fixes pierced mouse ears.

A laboratory mishap has revealed a super-healing mouse, a rare example of a mammal that regenerates complex, scar-free tissue.

In a matter of weeks, mice of a well-known laboratory strain called MRL can regrow perfect tissue, including cartilage, to close large holes punched in their ears, reports immunologist Ellen Heber-Katz of the Wistar Institute in Philadelphia. Other mice just heal around the rim, leaving the hole open.

The MRL mouse may provide a new way of studying regeneration, says Heber-Katz, possibly taking researchers a step closer to realizing the dream of enabling people to regrow lost limbs. She described her group's findings in Philadelphia last week at the annual meeting of the American Association for the Advancement of Science. A full account is scheduled to appear in Clinical Immunology and Immunopathology.

Researchers customarily put holes in the ears of laboratory mice to identify them. One day, Heber-Katz was horrified to notice that a number of MRL mice being used in a study of multiple sclerosis had no holes in their ears. The scientist responsible for marking the mice was certain she hadn't forgotten this essential step. The puzzled researchers once again punched holes in the animals' ears. The holes closed in about 3 weeks.

After attending a lecture on regeneration in amphibians, "I realized that [regeneration] was exactly what we were seeing," Heber-Katz says. She later learned that other researchers had noticed the quirk in mice, but she found no systematic investigations of it.

While studying sections of ear tissue at various stages of recovery, Heber-Katz observed hallmarks not just of wound repair but also of true regeneration. She found blastemas, blobs of rapidly dividing immature cells, and evidence that a key protein layer, the extracellular matrix, breaks down, allowing tissues to regrow.

That process has a lot of similarities to what we see in amphibians," says David L. Stocum at indiana University-Purdue University in Indianapolis.

In general, amphibians far outstrip mammals when it comes to regenerative powers (SN: 11/1/97, p. 280). People do manage to recreate some tissues, like bone, if an injury is not too severe. On rare occasions, severed fingertips regrow. Moose, elk, and deer resprout antlers, and rabbits can repair ear holes, like the MRL mice.

Heber-Katz noticed that regenerative powers in mice dwindle with age. When she injected old mice with antibodies that block receptors for immune system components known as alphabeta T cells, the elders could regrow tissue like any youngster. When the scientists genetically engineered mice to lack the genes for these receptors, the animals regenerated the tissue far better than normal.

The T cell system may choke off regeneration, Heber-Katz says. She speculates that mammals may have paid a heavy price -- the power to regenerate -- when their deluxe immune systems developed.