Featured Research

from universities, journals, and other organizations

Gene variant exacerbates inflammatory arthritis in mice

Date:
December 16, 2013
Source:
University of Utah Health Sciences
Summary:
Researchers have discovered a naturally occurring genetic variation in mice that predisposes carriers toward developing severe, inflammatory arthritis.

Severe arthritis in mouse joint.
Credit: University of Utah

University of Utah researchers have discovered a naturally occurring genetic variation in mice that predisposes carriers toward developing severe, inflammatory arthritis. The finding implicates a new class of genes in arthritis progression, potentially opening doors to new treatment options. The study will be published ahead of print on Dec. 16 in the online issue of The Journal of Clinical Investigation.

Among individuals with inflammatory arthritis, the severity of symptoms, which include joint swelling, pain, and stiffness, varies greatly. The phenomenon is readily apparent among patients of Lyme disease, caused by a bacterial infection that is transmitted by ticks. Despite antibiotic treatment, up to 10 percent of patients will develop chronic Lyme arthritis.

"We were hoping to identify genes and physiological pathways responsible for the differences in arthritis severity, with an eventual goal of identifying potential therapeutic interventions," says Janis Weis, Ph.D., U of U professor of pathology and senior author on the study.

Weis' investigation began after learning that, similar to what is observed in people, a strain of mice called C3H develops severe arthritis with Lyme disease, while a different strain, B6, develops mild symptoms. Because the mice are highly inbred, mice in each strain are near genetic carbon copies of one another. This feature has allowed her group to cross the two strains, progressively narrowing down regions of C3H DNA that confer arthritis susceptibility in offspring.

A result 20 years in the making, her group arrived at a single base pair change, or polymorphism, in the gene - glucuronidase (Gusb) that they call Gusbh. Gusbh mice not only develop severe arthritis symptoms in response to Lyme disease, but also to a rheumatoid arthritis-like condition. This finding implicates that the protein encoded by Gusb is a contributor to two types of inflammatory arthritis, expanding the potential impact to a larger group of arthritis patients.

The GUSB protein is an enzyme that resides in the lysosome, often considered the "stomach" of the cell. There, the enzyme breaks down complex carbohydrates called glycosaminoglycans (GAGs).

Until now, there were no clues as to how this type of protein might regulate arthritis progression. "All we knew is that Gusb is a housekeeping gene that carries out the nuts and bolts activities in the cell," says Kenneth Bramwell, Ph.D., postdoctoral fellow Weis' lab and lead author on the study. "We had our work cut out for us."

The study shows that Gusbh causes an amino acid change that lowers the enzymatic activity of the protein by up to 90 percent. Consistent with the observation, GAGs fail to be broken down in Gusbh mice with inflammatory arthritis, and accumulate at sites of inflammation. These findings suggest that the build-up of GAGs is a contributing factor to the development of severe arthritis.

"These [GAGs] may be activating the innate immune response. That's one possibility. It could be that GAGs are deposited in response to this infection and that that contributes to a more severe disease trajectory," says Bramwell. Future studies will focus on understanding the mechanism, with the intention of identifying new ways to halt disease progression.

This is the first time that a lysosomal storage enzyme has been implicated in the development of arthritis. The discovery reveals the possibility that GUSB or the 40 other members of this class of proteins may also be involved in the progression of arthritis in people.

"The doctors that we've spoken to who have familiarity with rheumatoid arthritis are quite excited by these findings," says Bramwell.


Story Source:

The above story is based on materials provided by University of Utah Health Sciences. Note: Materials may be edited for content and length.


Journal Reference:

  1. Kenneth K.C. Bramwell, Ying Ma, John H. Weis, Xinjian Chen, James F. Zachary, Cory Teuscher, Janis J. Weis. Lysosomal β-glucuronidase regulates Lyme and rheumatoid arthritis severity. Journal of Clinical Investigation, 2013; DOI: 10.1172/JCI72339

Cite This Page:

University of Utah Health Sciences. "Gene variant exacerbates inflammatory arthritis in mice." ScienceDaily. ScienceDaily, 16 December 2013. <www.sciencedaily.com/releases/2013/12/131216142006.htm>.
University of Utah Health Sciences. (2013, December 16). Gene variant exacerbates inflammatory arthritis in mice. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2013/12/131216142006.htm
University of Utah Health Sciences. "Gene variant exacerbates inflammatory arthritis in mice." ScienceDaily. www.sciencedaily.com/releases/2013/12/131216142006.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com
Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins