Mouse Mutant Resource turns 50

It is difficult to overstate the scientific value of the Laboratory's Mouse Mutant Resource (MMR) program. Now entering its 50th year, the program has built a unique repository of naturally occurring mutations that has greatly assisted research into a wide variety of human diseases, including obesity, diabetes, heart disease, neurological disorders and more.

"People have genetic disorders because of mutations—something that has gone wrong in their chromosomes," says Muriel Davisson, Ph.D., a Jackson Laboratory professor whose research over the last 37 years has relied heavily on naturally occurring lab mouse mutations. "Through the MMR, we're discovering [disease] models that occur through the same spontaneous processes that occur in people."

New technologies that allow researchers to develop targeted mutations can supplement, but not replace, the spontaneous mutants.

"These are complementary strategies that need to be sustained on a parallel basis," says Davisson. "Each comes with its own advantages."

Challenge gift to attract, support new faculty

Geneticist and author Weslie Janeway of New York has made a $1 million "challenge gift" to the Laboratory for the recruitment and support of new scientists working to understand the genetic basis of human disease. The challenge gift is intended to encourage $1 million in matching gifts from other donors.

"A secure funding base is necessary to attract outstanding researchers," says Janeway, a Laboratory trustee. "This represents the best possible investment in the future of The Jackson Laboratory."

The gift arrives as the Laboratory embarks on a five-year strategic plan to expand its faculty to 45 principal investigators from the current 38 by 2014.

"Mrs. Janeway's generous gift will help us attract bright young faculty with new ideas and approaches to enhance our genetics research at the Laboratory," says Richard Woychik, Ph.D., president and CEO of the Laboratory.

Stem cell technologies attract grant funding

The Jackson Laboratory recently received a $12,500 seed grant from the Maine Technology Institute to investigate new stem cell technologies.

In theory, stem cells can adapt and grow into any kind of tissue in the body. Using them to repair pancreas damage might reverse type 1 diabetes, or putting them to work regrowing heart tissue could restore function after a heart attack. Recent progress has yielded a way to convert adult cells into embryonic-like stem cells, potentially eliminating a wide range of ethical and technical problems associated with using embryonic stem cells.

Anne Greenlee, Ph.D., and Michael Wiles, Ph.D., will lead the project to see if the adult cells, called induced pluripotent stem (iPS) cells, do indeed function as embryonic stem cells would. According to Greenlee, "This will be an important step in establishing whether iPS cells could someday be harvested from an individual patient and used as a kind of 'replacement parts kit' for that patient's own diseased tissues."

Laboratory ranked second for postdocs

The Jackson Laboratory is among the nation's top institutions for scientists in the postdoctoral phase of their careers. The Laboratory was voted No. 2 in a poll of postdocs conducted by The Scientist, a magazine for people working in the life sciences, up from the No. 9 spot in 2008.

After completing their Ph.D.s, most young scientists find a postdoctoral research position under the mentorship of a principal investigator, a kind of apprenticeship before setting up their own laboratories. Jackson postdocs participating in the survey cited training, mentoring and funding as the institution's greatest workplace strengths. The results of the survey were published in the March edition of The Scientist.

In November, The Jackson Laboratory was also listed among the top 20 in The Scientist's "Best Places to Work in Academia" poll.

Former Jackson researchers highlighted in The Scientist

Genetics and molecular biology are now so intertwined that it's easy to forget that not long ago they were regarded as two separate topics. In 1980 it was unusual for a molecular biologist to want to work at The Jackson Laboratory, long a pre-eminent hub for genetics research. But as profiled in the February issue of The Scientist, Nancy Jenkins, Ph.D., and her husband/collaborator Neal Copeland, Ph.D., were among the first to bring modern molecular biology techniques to bear on genetics problems, building a formidable list of contributions to human disease research based on their work at the Laboratory.

Jenkins and Copeland used viruses that carry RNA, known as retroviruses, as their primary tools. Retroviruses produce DNA in the host cells, which then integrates into the host's genome, sometimes producing disease-causing mutations. Jenkins and Copeland used retroviruses to identify and clone genes, with a particular focus on cancer-causing genes, and their work at the Laboratory throughout the 1980s greatly improved genetics research techniques. They now work at Singapore's Institute of Molecular and Cell Biology, but their time at the Laboratory remains why they are described as "the founders of modern mouse genetics."

Jackson Laboratory researchers seek root causes of lupus

Systemic lupus erythematosus (SLE) in humans is a chronic, multigenic autoimmune disease characterized by a wide spectrum of clinical abnormalities. SLE affects more than 2 million Americans—90 percent of them women—with symptoms that include joint pain, extreme fatigue and renal disease. The cause of SLE is not well understood.

The primary job of the immune system is to identify and vanquish potentially dangerous infectious pathogens. Autoimmune diseases develop when the immune system instead unleashes this potent defense system against the individual's own tissues, with predictably severe consequences.

In a recent paper (Proceedings of the National Academy of Sciences, February 3, 2009), researchers led by Jackson Laboratory Professor Derry Roopenian, Ph.D., and Postdoctoral Associate Jason Bubier, Ph.D., present evidence for a possible root cause of lupus and hope for better therapies. They focused on interleukin 21 (IL-21), an important component of immune system signaling. However, IL-21 produced in overabundance by individuals susceptible to SLE can cause the defense mechanism to misfire and produce antibodies that attack the individual's own tissues.

"The findings provide a strong clue towards understanding how SLE occurs and a clear indication of the importance of interleukin 21 signaling in lupus-like diseases," says Roopenian. "They suggest that interrupting interleukin 21 signaling events may prove to be an effective therapeutic option for human SLE."

Study: Calorie restriction helps only obese mice live longer

A small but dedicated group of people eats very little in a quest to live longer. Research in a variety of laboratory animals and even a recent human study indicated that caloric restriction improves longevity. But does a calorie-restricted diet actually lengthen your life? Probably not, unless you're already overweight, say scientists at the University of Southern California and North Texas Health Science Center.

The scientists studied two strains of JAX® Mice from The Jackson Laboratory to see whether subjecting them to a low-calorie diet prolonged their life span by lowering the rate of metabolism. The C57BL/6J mouse tends to gain weight throughout its lifetime, while the DBA/2J mouse stays lean.

The results, recently published in the Journal of Nutrition, showed that while calorie restriction did lower the metabolic rate in both strains, there was no effect on the life span of the DBA mice when compared to DBA mice that were allowed to eat as much as they wanted. The "dieting" C57BL mice did live longer than their free-feeding peers, but the researchers attributed that to the diet's returning the animals to a state of balance between their energy intake and energy expenditure.