Genetic observation reveals a bone-weakening mechanism

August 31, 2012
Genetic observation reveals a bone-weakening mechanism
Bone structure and firmness partly rely on some genes. © Inserm - Daniel Chappard

(Medical Xpress)—An EPFL research team has used a novel method to identify a gene involved in bone building. Their results appear today in the advance online edition of the scientific journal Cell.

"Real life genetics" works. This research method involves observing physiological traits or in a large population of "wild-type" mice (those which have not been genetically modified), and then isolating the genes that could be responsible. Because it's complex and expensive, the method is rarely used, but it has nonetheless enabled EPFL researchers to obtain interesting results.

An article published today in the online edition of the journal Cell describes how the method was used to reveal a dysfunctional process. "We compared the genotype of mice with a fragile with mice that were more robust," explains Evan Williams, a scientist in EPFL's Laboratory for Integrative and Systemic Physiology (LISP). "By observing their genes, we were able to identify the one responsible for alkaline phosphatase (ALPL), whose malfunction leads to various forms of ."

A factor in osteoporosis

Scientists were already familiar with hypophosphatase, a human disease caused by the absence of this gene that leads to extreme skeletal fragility from a very young age. "With this new discovery we can conclude that a defect in the for alkaline phosphatase affects in . In fact, fractures are the primary cause for hospitalization in the elderly," says LISP director Johan Auwerx. Pénélope Andreux, a co-author of the study, adds that the gene has other jobs in the cell as well: "it plays an important role in absorption, which is involved in protein metabolism," she explains.

Very different characteristics

These results suggest that new therapeutic avenues might be possible for preventing osteoporosis, by acting on the enzymes associated with the expression of this gene. But that's not all. The study of this population of mice wasn't limited to their bones: no less than 140 parameters, such as body weight, running speed and fur color, were measured, and the results were often astonishing.

For example, in a single population and without any added stimulation, some mice spontaneously ran two km every night, while others ran twelve. And some mice had up to 6.7 times better glucose tolerance than others.

What could explain these differences? "Our results, which we have made available to the scientific community, will allow specialists in various fields to make associations between the genome of these mice and their physical and behavioral characteristics," says Auwerx. "Then it will be a matter of establishing correlations with the expression of the same genes in humans." Observing these mice populations will thus lead to many discoveries.

Explore further: Tweaking a gene makes muscles twice as strong

More information: Pénélope A. Andreux, Evan G. Williams et al., Systems Genetics of Metabolism : The Use of the BXD Murine Reference Panel for Multiscalar Integration of Traits. Cell, dx.doi.org/10.1016/j.cell.2012.08.012

Related Stories

Tweaking a gene makes muscles twice as strong

November 10, 2011
A team of researchers at EPFL, the University of Lausanne and the Salk Institute created super strong, marathon mice and nematodes by reducing the function of a natural inhibitor, suggesting treatments for age-related or ...

An important breakthrough at the IRCM associated with osteoporosis

October 4, 2011
Researchers at the Institut de recherches cliniques de Montréal (IRCM), directed by Dr. Jean Vacher, identified a new gene that modulates bone mass and that could become a risk factor for developing osteoporosis. This ...

Bile acids may hold clue to treat heart disease

December 6, 2011
Heart disease is a major cause of death in industrialised countries, and is strongly associated with obesity and diabetes. Many scientists believe that what links these conditions is a chronic, low-grade inflammation. The ...

Researcher discovers epigenetic links in cell-fate decisions of adult stem cells

July 9, 2012
(Medical Xpress) -- The ability to control whether certain stem cells ultimately become bone cells holds great promise for regenerative medicine and potential therapies aimed at treating metabolic bone diseases.

Recommended for you

Team finds link between backup immune defense, mutation seen in Crohn's disease

July 27, 2017
Genes that regulate a cellular recycling system called autophagy are commonly mutated in Crohn's disease patients, though the link between biological housekeeping and inflammatory bowel disease remained a mystery. Now, researchers ...

Study finds harmful protein on acid triggers a life-threatening disease

July 27, 2017
Using an array of modern biochemical and structural biology techniques, researchers from Boston University School of Medicine (BUSM) have begun to unravel the mystery of how acidity influences a small protein called serum ...

CRISPR sheds light on rare pediatric bone marrow failure syndrome

July 27, 2017
Using the gene editing technology CRISPR, scientists have shed light on a rare, sometimes fatal syndrome that causes children to gradually lose the ability to manufacture vital blood cells.

Post-stroke patients reach terra firma with new exosuit technology

July 26, 2017
Upright walking on two legs is a defining trait in humans, enabling them to move very efficiently throughout their environment. This can all change in the blink of an eye when a stroke occurs. In about 80% of patients post-stroke, ...

Molecular hitchhiker on human protein signals tumors to self-destruct

July 24, 2017
Powerful molecules can hitch rides on a plentiful human protein and signal tumors to self-destruct, a team of Vanderbilt University engineers found.

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.