New insights into limb formation

Aug 12, 2009

Investigators at Burnham Institute for Medical Research (Burnham) and the University of Connecticut Health Center (U.C.H.C.) have gained new understanding of the role hyaluronic acid (HA) plays in skeletal growth, chondrocyte maturation and joint formation in developing limbs. Significantly, these discoveries were made using a novel mouse model in which the production of HA is blocked in a tissue-specific manner.

The Yamaguchi laboratory genetically modified the Has2 gene, which is a critical for HA synthesis, so that the gene can be "conditionally" disrupted in mice. This is the first time a conditional Has2 knockout mouse has been created, a breakthrough that opens vast possibilities for future research. The paper was published online in the journal Development on July 24.

HA is a large that is produced by every cell in the body and has been thought to play a role in joint disease, heart disease and invasive cancers. Yu Yamaguchi, M.D., Ph.D., a professor in the Sanford Children's Health Research Center at Burnham and Robert Kosher, Ph.D., a professor in the Center for Regenerative Medicine and Skeletal Development at U.C.H.C. and colleagues showed that , in which Has2 was inactivated in the bud mesoderm, had shortened limbs, abnormal growth plates and duplicated bones in the fingers and toes.

"Because hyaluronic acid is so prevalent in the body, it has been difficult to study," said Dr. Yamaguchi. "Systemic Has2 knockout mice died mid-gestation and could not be used to study the role of HA in adults. By inactivating Has2 in specific tissues, we give ourselves the opportunity to study the many roles HA plays in biology. This mouse model will be useful to study the role of HA in various age-related diseases and conditions, such as arthritis and skin aging, as well as cancer."

To create the conditional knockout mice, the Yamaguchi laboratory genetically engineered the Has2 gene to create the Has2flox allele. The team then added the Prxl1-Cre transgene, which is associated with early limb bud mesenchyme to produce the conditional Has2 knockout mice.

Source: Burnham Institute (news : web)

Explore further: Platelets modulate clotting behavior by 'feeling' their surroundings

add to favorites email to friend print save as pdf

Related Stories

Embryology study offers clues to birth defects (w/Video)

Jun 09, 2009

Gregg Duester, Ph.D., professor of developmental biology at Burnham Institute for Medical Research (Burnham), along with Xianling Zhao, Ph.D., and colleagues, have clarified the role that retinoic acid plays in limb development. ...

A Mouse for Every Gene

Sep 07, 2006

The University of California, Davis, will play a key role in a new worldwide effort to create a so-called "knockout" mutant mouse for each of the approximately 20,000 genes in the mouse genome. These mice can be used to study ...

Stem cell research uncovers mechanism for type 2 diabetes

Feb 12, 2009

Taking clues from their stem cell research, investigators at the University of California San Diego (UC San Diego) and Burnham Institute for Medical Research (Burnham) have discovered that a signaling pathway involved in ...

Recommended for you

A better way to track emerging cell therapies using MRIs

Sep 19, 2014

Cellular therapeutics – using intact cells to treat and cure disease – is a hugely promising new approach in medicine but it is hindered by the inability of doctors and scientists to effectively track the movements, destination ...

User comments : 0