Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene gives clues to self-injurious behavior in rare disorder

28.07.2011
In humans, inherited mutations in a gene called HPRT1 lead to very specific self-destructive behavior. Boys with Lesch-Nyhan disease experience uncontrollable urges to bite their fingers, slam their arms into doorways and otherwise harm themselves.

Puzzlingly, mice with mutations in the same gene don't behave differently than normal mice. Researchers at Emory University School of Medicine have identified a gene related to HPRT1, present in humans but not in mice that helps explain this discrepancy.

The results were published this week by the journal PLoS One.

Mice missing HPRT1 and engineered with a copy of the related human gene, called PRTFDC1, are more aggressive and, under the influence of amphetamines, display repetitive behavior resembling nail biting.

"Other strains of mice don't do this, even under the influence of amphetamines," says first author Alaine Keebaugh, an Emory postdoctoral fellow. "It's not exactly the same as the finger-biting seen in Lesch-Nyhan patients, but they're close enough that we think it provides some insight into the biology. It suggests that PRTFDC1 could be a target for treating the disease."

Keebaugh began researching HPRT1 and PRTFDC1 while a graduate student in the laboratory of James Thomas, PhD, former assistant professor of human genetics at Emory University School of Medicine. The co-first author is Emory postdoctoral fellow Heather Mitchell.

HPRT1 was the first gene to be "knocked out" when scientists were first developing the technique in the 1980s, an accomplishment that earned Mario Capecchi and Oliver Smithies the Nobel Prize in Medicine.

"HPRT1 has a special place in the history of genetics because of this," Keebaugh says. "It also shows that knockout mice don't always exactly parallel human disease."

The HPRT1 gene is located on the X chromosome. Males are vulnerable to Lesch-Nyhan disease (and other X-linked disorders) because they have only one X chromosome. HPRT1 encodes an enzyme that recycles purines, which are building blocks of DNA.

The PRTFDC1 gene looks like HPRT1, and apparently comes from a duplication of an ancestor gene millions of years ago. All mammals Keebaugh examined except mice have working copies of PRTFDC1. It's not clear whether the protein encoded by PRTFDC1 also recycles purines, she says.

"In mice, the presence of PRTFDC1 seems to enhance the effects of not having HPRT1," she says. "This suggests the two proteins are not just doing the same things. One may be regulating the other, which is something we want to investigate further."

In humans, the absence of HPRT1 leads to overabundant purines, which appears to perturb development of certain parts of the brain. In addition, the building blocks are broken down into uric acid, which accumulates in the body and can cause painful swelling of the joints.

These gout-like symptoms can be treated with medication, but the striking behavior and other neurological problems don't go away. Lesch-Nyhan patients tend to have delayed development and stiff movements and are sometimes unable to walk. They have a deficiency of the chemical messenger dopamine in the basal ganglia, the same part of the brain affected by Parkinson's disease.

Mice without HPRT1 do have reduced dopamine in the basal ganglia and are more sensitive to amphetamines, which work by enhancing dopamine's effects in the brain. This link with dopamine is what led Keebaugh to test the effects of amphetamines on the mice.

Mice missing HPRT1 and with added PRTFDC1 displayed a unique behavior: they had a "distinctive hunched posture," bobbing their heads and appearing to bite their nails. However, they did not actually damage their paws.

Keebaugh says she is continuing to study the function of PRTFDC1 with the aim of understanding how Lesch-Nyhan disease develops and identifying potential treatments.

The research was supported by the National Institutes of Health.

Reference: A.C. Keebaugh, H.A. Mitchell, M. Gaval-Cruz, K.G. Freeman, G.L. Edwards, D. Weinshenker, and J.W. Thomas. PRTFDC1 is a genetic modifier of HPRT-deficiency in the mouse. PLOS One (2011).

Writer: Quinn Eastman

Holly Korschun | EurekAlert!
Further information:
http://www.emory.edu

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>