Featured Research

from universities, journals, and other organizations

New mouse model may provide inroads to understanding severe genetic disorder in children

Date:
September 20, 2012
Source:
American Thyroid Association
Summary:
New mouse models can help scientists study MCT8 deficiency, an inherited genetic disorder affecting children, according to new data.

New mouse models can help scientists study MCT8 deficiency, an inherited genetic disorder affecting children, according to new data presented at the 82nd Annual Meeting of the American Thyroid Association (ATA) in Québec City, Québec, Canada.

Related Articles


"MCT8 deficiency is a serious diagnosis. Children born with this inherited disorder experience profound psycho-motor delays and are often completely incapacitated," said Douglas Forrest, PhD, of the National Institute of Diabetes and Digestive and Kidney Diseases, and Program Co-Chair of the ATA Annual Meeting. "New ways to study this disorder are greatly needed."

MCT8 deficiency (MCT8-specific Thyroid Hormone Cell Transporter Deficiency) is a rare genetic condition that affects mostly males. Children with MCT8 deficiencies often experience severe developmental delays, poor head control, low muscle tone, and unclear or no speech. MCT8 deficiency is caused by a mutation in the MCT8 (Monocarboxylate transporter 8) gene. In mice, Mct8 deficiency results in an impaired transport of T3, but not of T4 into the brain, and it is not associated with any neurological impairments.

To learn more about MCT8 deficiency, a team of researchers led by Steffen Mayerl, a PhD candidate in the lab of Heike Heuer, PhD, at the Leibniz Institute for Age Research/Fritz Lipmann Institute, in Jena, Germany, thus speculated that in mice, TH uptake into the CNS is facilitated by Mct8 and by Oatp1c1, a T4-specific TH transporter localized at the blood-brain barrier. To define the role of Mct8 and Oatp1c1 in brain TH transport, they began by generating Mct8/Oatp1c1 double knockout (dko) mice and analyzing them by determining T4 transport, brain TH content, deiodinase activities, and expression levels of TH-regulated gene products in wild type, the respective single and double mutant animals. They performed immunohistochemical stainings to determine neuronal differentiation and myelination at different postnatal timepoints. The mice were also subjected to extensive behavioral studies.

They found that, in contrast to Mct8 ko and Oatp1c1 ko mice, Mct8/Oatp1c1 dko mice exhibited a strongly diminished uptake of T4 into the CNS. Hence, brain T4 and T3 content was pronouncedly reduced, while type 2 deiodinase activities were found to be highly elevated. Determination of T3-regulated gene products indicated a severe hypothyroid state of the brain in the absence of both transporters. As a consequence, differentiation of inhibitory neurons in the cerebral cortex, as well as myelination, was strongly impaired. Finally, behavior tests revealed coordination and locomotor deficits in Mct8/Oatp1c1 dko mice.

These data point to a critical function of Mct8 and Oatp1c1 in the transport of TH into the brain. Since Oatp1c1 is only weakly expressed in the human CNS, Mct8/Oatp1c1 dko mice may be considered as an animal model for human MCT8 deficiency.


Story Source:

The above story is based on materials provided by American Thyroid Association. Note: Materials may be edited for content and length.


Cite This Page:

American Thyroid Association. "New mouse model may provide inroads to understanding severe genetic disorder in children." ScienceDaily. ScienceDaily, 20 September 2012. <www.sciencedaily.com/releases/2012/09/120920115638.htm>.
American Thyroid Association. (2012, September 20). New mouse model may provide inroads to understanding severe genetic disorder in children. ScienceDaily. Retrieved October 24, 2014 from www.sciencedaily.com/releases/2012/09/120920115638.htm
American Thyroid Association. "New mouse model may provide inroads to understanding severe genetic disorder in children." ScienceDaily. www.sciencedaily.com/releases/2012/09/120920115638.htm (accessed October 24, 2014).

Share This



More Health & Medicine News

Friday, October 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Breakfast Debate: To Eat Or Not To Eat?

Breakfast Debate: To Eat Or Not To Eat?

Newsy (Oct. 23, 2014) — Conflicting studies published in the same week re-ignited the debate over whether we should be eating breakfast. Video provided by Newsy
Powered by NewsLook.com
Ebola Fears Keep Guinea Hospitals Empty

Ebola Fears Keep Guinea Hospitals Empty

AP (Oct. 23, 2014) — Fears of Ebola are keeping doctors and patients alike away from hospitals in the West African nation of Guinea. (Oct. 23) Video provided by AP
Powered by NewsLook.com
Despite Rising Death Toll, Many Survive Ebola

Despite Rising Death Toll, Many Survive Ebola

AP (Oct. 23, 2014) — The family of a Dallas nurse infected with Ebola in the US says doctors can no longer detect the virus in her. Despite the mounting death toll in West Africa, there are survivors there too. (Oct. 23) Video provided by AP
Powered by NewsLook.com
Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) — Is your child ready? Video provided by Working Mother
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:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

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