Featured Research

from universities, journals, and other organizations

Mouse Brain Tumors Mimic Those In Human Genetic Disorder

Date:
January 13, 2005
Source:
Washington University School Of Medicine
Summary:
A recently developed mouse model of brain tumors common in the genetic disorder neurofibromatosis 1 (NF1) successfully mimics the human condition and provides unique insight into tumor development, diagnosis and treatment, according to researchers at Washington University School of Medicine in St. Louis.

Dec. 29, 2004 — A recently developed mouse model of brain tumors common in the genetic disorder neurofibromatosis 1 (NF1) successfully mimics the human condition and provides unique insight into tumor development, diagnosis and treatment, according to researchers at Washington University School of Medicine in St. Louis.

After validating their animal model, the team made two important discoveries: New blood vessels and immune system cells may be essential to the initial formation of tumors and therefore may be promising drug targets; and brain images often used to determine the need for treatment may not actually be diagnostically informative.

"These mice develop brain tumors with many of the same features as those seen in children with NF1, and studying those tumors has helped us understand the cellular events involved in NF1 brain tumor development," says principal investigator David H. Gutmann, M.D., Ph.D., the Donald O. Schnuck Family Professor of Neurology.

The study appears online and will be published in the January 2005 issue of the journal Annals of Neurology.

NF1 is one of the most common neurological disorders caused by a single gene mutation. The disorder can lead to a variety of complications including brain cancer.

To supplement their clinical research, Gutmann's team developed a mouse model in which the animals, like humans with the disease, have one abnormal copy of the gene for NF1 in every cell in their body, while specific support cells in the brain called astrocytes have two abnormal copies of this same gene.

Their latest paper shows that brain tumor formation in these mice has several of the same distinguishing clinical characteristics as tumor development in children with NF1.

First, the mice developed tumors along the optic nerve and optic chiasm, which transmit visual information from the eye to the brain. This type of tumor, called an optic pathway glioma, is the most common tumor in children with NF1.

Second, the time course of tumor development was similar to that seen in humans. Unlike most tumors, optic pathway gliomas associated with NF1 typically stop growing after a few years. Moreover, they almost always occur in children — these tumors generally start growing in children younger than 5 years old and usually do not progress after age 10. A similar pattern occurred in the mice: The optic nerve and chiasm were enlarged and astrocytes along the optic pathway began multiplying and growing when the animals were around three weeks old, developing into optic pathway gliomas by two months of age. After that time-period, which is roughly equivalent to teenage years in humans, the cells slowed down to the same growth speed as astrocytes in control mice.

"The fact that cell growth is dramatically reduced after a few months in mice and after a few years in humans tells us there may be growth signals that are produced early in life, which are critical for tumor formation and expansion," Gutmann explains.

Optic pathway gliomas in humans are typically surrounded by blood vessels and microglia, which are immune system cells in the brain. But it was unclear whether the development of blood vessels and recruitment of microglia helped trigger tumor formation or if they appeared only after the tumor was fully developed. The researchers found that by three weeks of age, the mutant mice had about four times the number of small blood vessels in the optic nerves and chiasm as control mice. Similarly, microglia were also found in the nerve and chiasm of mutant mice prior to tumor formation.

"In our judgment, the fact that recruitment of new blood vessels and infiltration of immune system cells occurs before actual tumor formation suggests that these events are important for the development of tumors," Gutmann says. "These findings raise the possibility that targeted therapies for NF1 brain tumors may involve agents that prevent the supply of growth promoting factors provided by new blood vessels and microglia."

Next, the researchers used the mouse model to investigate a clinical concern. Physicians rely on several tests to determine whether a child with an optic pathway glioma should undergo treatment for the tumor, including the tumor's size and the patient's clinical symptoms. But often those tests aren't sufficiently informative, so experts also examine pictures of the patient's brain taken with magnetic resonance imaging (MRI). To capture such brain images, physicians inject a contrast dye into a patient's bloodstream and look for accumulation of dye around the tumor. Though dye accumulation may be a sign of tumor progression, it is unclear whether that is always the case, particularly in optic pathway gliomas associated with NF1.

Results from this latest study suggest that the two are not necessarily correlated. Gutmann's team found that optic pathway gliomas lit up just as brightly in 2-month-old mice as in 8-month-old mice, despite the fact that the tumors were actively growing only in the younger mice.

"If this finding is also true in humans, this strongly argues that contrast enhancement on MRI alone is not a reliable test of tumor progression," Gutmann says. "If we rely on contrast enhancement in children with NF1 optic pathway gliomas, we may be treating kids who don't need to be treated. Using this mouse model, we hope to continue to hone in on more accurate diagnostic, prognostic and treatment approaches."

Bajenaru ML, Garbow JR, Perry A, Hernandez MR, Gutmann DH. Natural history of neurofibromatosis 1-associated optic nerve glioma formation in mice. Annals of Neurology, January 2005.

Funding from the National Institutes of Health, the United States Department of Defense, the National Cancer Institute, the Alvin J. Siteman Cancer Center and the National Eye Institute supported this research.

Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked second in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.


Story Source:

The above story is based on materials provided by Washington University School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School Of Medicine. "Mouse Brain Tumors Mimic Those In Human Genetic Disorder." ScienceDaily. ScienceDaily, 13 January 2005. <www.sciencedaily.com/releases/2005/01/050110121821.htm>.
Washington University School Of Medicine. (2005, January 13). Mouse Brain Tumors Mimic Those In Human Genetic Disorder. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2005/01/050110121821.htm
Washington University School Of Medicine. "Mouse Brain Tumors Mimic Those In Human Genetic Disorder." ScienceDaily. www.sciencedaily.com/releases/2005/01/050110121821.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Despite Health Questions, E-Cigs Are Beneficial: Study

Despite Health Questions, E-Cigs Are Beneficial: Study

Newsy (July 31, 2014) Citing 81 previous studies, new research out of London suggests the benefits of smoking e-cigarettes instead of regular ones outweighs the risks. Video provided by Newsy
Powered by NewsLook.com
Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
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