Jackson Lab IDs gene linked to degeneration

Jackson Laboratory researchers have identified a gene in a strain of mice that apparently protects the brain against neurological degeneration seen in disorders such as Lou Gehrig’s disease.

The journal Nature, which published a report on the work in the issue to be released today, said in a statement that the discovery will give a “boost” to research into age-related decline in thought and judgment. It also said that the research team’s discovery of certain cell functions related to neurological degeneration may allow development of new therapies to slow or stop such damaging cell activities.

The neurological degeneration stems from a process that includes either an overproduction of molecules having an unstable form of oxygen or an underproduction of antioxidants intended to counteract those molecules.

The unstable molecules, commonly referred to as free radicals, are normally created as a byproduct of cells making energy. However, should the production of the free radicals or the level of antioxidants get out of whack, the free radicals begin to damage cells.

The damage can lead to cell death. This process, called “oxidative stress,” is thought to play a major role not only in Lou Gehrig’s disease but also in a variety of other problems such as cancer, heart disease and wrinkled skin.

The scientists found the gene that protects certain brain and retinal neurons from oxidative stress in the “harlequin mouse,” a strain with a mottled coat.

Jackson Laboratory staff scientist Susan Ackerman, who led the research team, said the team also identified an important intermediary process between the elevation of unchecked free radicals and the death of nerve cells. Once oxidative stress begins to affect the nerve cells, they try to duplicate their DNA in a process called “re-entering the cell cycle.”

The re-entering the cell cycle process has been noted in recent autopsies of the brains of some Alzheimer’s victims, Ackerman said. Jackson Laboratory found the first evidence of this in the retina. The finding shows that the process correlates with oxidative stress.

The discovery raises questions about whether a possible therapy could stop the cell cycle re-entry. Ackerman said researchers are also interested in why some neurons in the mice being studied were protected from oxidative stress damage, while others died. That suggests that there may be an additional protective function within those neurons, she said.

The harlequin mouse will now be a model for studying oxidative stress, cell cycle re-entry and the death of neurons.

The laboratory, a world-renowned genetics research facility in Bar Harbor, maintains more than 2,700 different strains of mice that it sells to scientific researchers around the world.