Featured Research

from universities, journals, and other organizations

New Mouse Model Of Inflammatory Bowel Disease Created And Successfully Treated

Date:
March 8, 2008
Source:
Washington University in St. Louis
Summary:
Researchers trying to improve cancer immune therapy have made an unexpected find: They've produced the most accurate mouse model to date of inflammatory bowel disease, a cluster of conditions that afflict approximately 1.4 million Americans with abdominal pain, constipation and diarrhea.

Researchers trying to improve cancer immune therapy have made an unexpected find: They've produced the most accurate mouse model to date of inflammatory bowel disease (IBD), a cluster of conditions that afflict approximately 1.4 million Americans with abdominal pain, constipation and diarrhea.

The two most common forms of IBD are Crohn's disease and ulcerative colitis (UC); in extreme cases, they can be fatal. The mouse model closely resembles the most serious form of human UC and is uniformly fatal. But scientists successfully treated the mice with a pair of broad-spectrum antibiotics, easing gut inflammation and increasing survival. The results, reported in Public Library of Science-Medicine, have researchers eager to follow up both in the clinic and the lab.

"The antibiotics we gave the mice were used individually in unsuccessful clinical trials as ulcerative colitis treatments, but now we have colleagues who are thinking of giving combined therapy an informal try," says co-senior author Thaddeus S. Stappenbeck, M.D., Ph.D., assistant professor of pathology and immunology and of developmental biology. "The antibiotics probably won't be a cure by themselves, but they may provide us with a potent new approach to combine with other therapies."

The mice may also allow scientists to learn which species of gut microorganisms are becoming embroiled in battles with host immune systems, triggering the symptoms of UC. That information could allow the development of stronger and more specific treatments.

Silvia Kang, a former graduate student in the laboratory of co-senior author Paul Allen, Ph.D., the Robert L. Kroc Professor of Pathology and Immunology, created the mouse model by crossbreeding two mouse lines they had developed for cancer immune therapy research. Each mouse line had one protein knocked out that restrained immune T cells from shifting into attack mode.

"The idea was to see if we could create super killer T cells we could use to attack tumors," says Allen. "But all the mice became sick early on, started to lose weight and we soon realized that they all had serious gastrointestinal issues."

Allen decided to consult with Stappenbeck, an expert in IBD.

"I've looked at quite a few proposed mouse models of IBD, and I recognized right away that this had the potential to be outstanding," says Stappenbeck. "The colons of the mice were incredible. They were filled with inflammatory T cells. We found the mice almost exactly replicated the most acute types of ulcerative colitis."

Unlike prior models of IBD, the mice consistently develop gastrointestinal problems within a short time period and at a predictable point in their lifespan. When researchers treated the mice at three weeks with the antibiotics ciprofloxacin and metronidazole, colon inflammation was reduced and the mice were able to gain weight and survive longer.

Scientists believe IBD results from the host immune system damaging the tissues of the gut while erroneously attacking food and gut microorganisms that aid food digestion. There are an estimated 500 different species of microbes living in the gut, so sorting out which species are being attacked by the immune system has been an imposing challenge.

The new model may significantly ease that challenge. Although the dual antibiotics used to treat the mice are broad-spectrum, they didn't sterilize the guts of the mice, suggesting that the treatment happened to eliminate the microorganisms causing IBD.

"We'd like to treat the mice and then reintroduce candidate microorganisms into their guts to see if this restarts the inflammatory reaction," says Stappenbeck.

Stappenbeck and Allen plan continued collaborative study of the model.

Journal reference: Kang SS, Bloom SM, Norian LA, Geske MJ, Flaveli RA, Stappenbeck TS, Allen PM. An antibiotic-responsive mouse model of fulminant ulcerative colitis. Public Library of Science-Medicine, March 3, 2008.

Funding from the National Institutes of Health and the Cancer Research Institute supported this research.


Story Source:

The above story is based on materials provided by Washington University in St. Louis. Note: Materials may be edited for content and length.


Cite This Page:

Washington University in St. Louis. "New Mouse Model Of Inflammatory Bowel Disease Created And Successfully Treated." ScienceDaily. ScienceDaily, 8 March 2008. <www.sciencedaily.com/releases/2008/03/080306115346.htm>.
Washington University in St. Louis. (2008, March 8). New Mouse Model Of Inflammatory Bowel Disease Created And Successfully Treated. ScienceDaily. Retrieved September 19, 2014 from www.sciencedaily.com/releases/2008/03/080306115346.htm
Washington University in St. Louis. "New Mouse Model Of Inflammatory Bowel Disease Created And Successfully Treated." ScienceDaily. www.sciencedaily.com/releases/2008/03/080306115346.htm (accessed September 19, 2014).

Share This



More Plants & Animals News

Friday, September 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Raw: Elephant Undergoes Surgery in Tbilisi Zoo

Raw: Elephant Undergoes Surgery in Tbilisi Zoo

AP (Sep. 18, 2014) Grand the elephant has successfully undergone surgery to remove a portion of infected tusk at Tbilisi Zoo in Georgia. British veterinary surgeons used an electric drill to extract the infected piece. (Sept. 18) Video provided by AP
Powered by NewsLook.com
Chimp Violence Study Renews Debate On Why They Kill

Chimp Violence Study Renews Debate On Why They Kill

Newsy (Sep. 17, 2014) The study weighs in on a debate over whether chimps are naturally violent or become that way due to human interference in the environment. Video provided by Newsy
Powered by NewsLook.com
Some Tobacco Farmers Thrive Amid Challenges

Some Tobacco Farmers Thrive Amid Challenges

AP (Sep. 16, 2014) The South's tobacco country is surviving, and even thriving in some cases, as demand overseas keeps growers in the fields of one of America's oldest cash crops. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Scientists Given Rare Glimpse of 350-Kilo Colossal Squid

Scientists Given Rare Glimpse of 350-Kilo Colossal Squid

AFP (Sep. 16, 2014) Scientists say a female colossal squid weighing an estimated 350 kilograms (770 lbs) and thought to be only the second intact specimen ever found was carrying eggs when discovered in the Antarctic. Duration: 00:47 Video provided by AFP
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