Breaking News
February 15, 2019 - Researchers uncover novel mechanism and potential new therapeutic target for Alzheimer’s
February 15, 2019 - Genetic variations in a fourth gene associated with higher ALL risk in Hispanic children
February 15, 2019 - Disruptive behavioral problems in kindergarten linked with lower employment earnings in adulthood
February 15, 2019 - New bioengineered device enhances the production of T-cells
February 15, 2019 - HDL proteome behaves like a tiny Velcro ball that is rolling on surfaces
February 15, 2019 - Puerto Rican children more likely to have poor or decreasing use of asthma inhalers
February 15, 2019 - Quality of patient care does not improve after physician-hospital integration
February 15, 2019 - Synopsys release new software for implant design and patient-specific planning
February 15, 2019 - 6 out of 10 hip replacements last 25 years or longer
February 15, 2019 - Health Tip: What You Should Know About Antibiotics
February 15, 2019 - New research challenges medical consensus that adenoids and tonsils significantly shrink during teenage years
February 15, 2019 - Discovery of weakness in a rare cancer could be exploited with drugs
February 15, 2019 - UVA scientists find potential explanation for mysterious cell death in Alzheimer’s, Parkinson’s
February 15, 2019 - New rules requiring female athletes to lower testosterone levels are based on flawed data
February 15, 2019 - Researchers comprehensively sequence the human immune system
February 15, 2019 - Researchers study animal venoms to identify new medicines for treating diseases
February 15, 2019 - Movement of wrist bones revealed by MRI and computer modeling
February 15, 2019 - Philips introduces new premium digital X-ray room to help shorten patient wait times
February 15, 2019 - Women fare worse than men following aortic heart surgery, study finds
February 15, 2019 - High-protein and low-calorie diet helps older adults lose weight safely, shows study
February 15, 2019 - Drug microdosing effects may not measure up to big expectations
February 15, 2019 - Discharged, Dismissed: ERs Often Miss Chance To Set Overdose Survivors On ‘Better Path’
February 15, 2019 - A digitized lab environment to be showcased at smartLAB 2019
February 15, 2019 - Scientists uncover main mechanisms of fluconazole drug resistance
February 15, 2019 - New study seeks to understand how colibactin causes cancer
February 15, 2019 - Photoacoustic imaging accurately measures the temperature of deep tissues
February 15, 2019 - Large study finds no association between phthalate exposure and breast cancer risk
February 15, 2019 - New research explains presence of ‘natural’ magnetism in human cells
February 15, 2019 - Bio-Rad launches new digital PCR system and kit for monitoring treatment response in CML patients
February 15, 2019 - Scientists shed light on damaging cell effects linked to aging
February 15, 2019 - High intensity exercise may improve health by increasing gut microbiota diversity
February 15, 2019 - Apellis’ APL-2 Receives Orphan Drug Designation from the FDA for the Treatment of Autoimmune Hemolytic Anemia
February 15, 2019 - Couples creating art or playing board games release ‘love hormone’
February 15, 2019 - Glimpsing The Future At Gargantuan Health Tech Showcase
February 15, 2019 - Common herbicide found to increase the risk of lymphoma
February 15, 2019 - Over-abundance of energy to cells could increase cancer risk
February 15, 2019 - Oxford Genetics appoints Jocelyne Bath as new Chief Operating Officer
February 15, 2019 - Castration-resistant metastatic prostate cancer responds to combination of immune checkpoint inhibitors
February 15, 2019 - Large-scale clinical trial begins to study liver transplantation between people with HIV
February 15, 2019 - Cannabis use among adolescents linked with increased risk of depression in adulthood
February 15, 2019 - Fractures, head injuries common in electric scooter accidents, UCLA study finds
February 15, 2019 - Prenatal maternal depression has important consequences for infant temperament, study shows
February 15, 2019 - Stereotactic body radiotherapy effective in treating men with low- or intermediate-risk prostate cancer
February 15, 2019 - Zogenix Submits New Drug Application to U.S. Food & Drug Administration for Fintepla for the Treatment of Dravet Syndrome
February 15, 2019 - Certain birthmarks warrant quick treatment, pediatricians say
February 15, 2019 - New machine learning method predicts if atypical ductal hyperplasia will turn cancerous
February 15, 2019 - Whole-genome sequencing and sharing real-time data could limit spread of foodborne bacteria
February 15, 2019 - FDA warns doctor for illegally marketing unapproved implantable device
February 15, 2019 - New injury documentation tool may provide better evidence for elder abuse cases
February 15, 2019 - Physiological age is a better predictor of survival than chronological age, shows study
February 15, 2019 - New study reveals high success rate for hip and knee replacements
February 15, 2019 - Prenatal exposures to BPA may pose threat to human ovarian function
February 15, 2019 - Suspicious spots on the lungs of children with rhabdomyosarcoma do not behave like metastases
February 15, 2019 - Diet drinks daily could raise stroke risk says study
February 15, 2019 - Many Systematic Reviews Do Not Fully Report Adverse Events
February 15, 2019 - Seven tips to protect your child from burns
February 15, 2019 - Keynote speakers announced for CBD Expo MIDWEST
February 15, 2019 - New DNA methylation GrimAge tool allows you to predict lifespan and healthspan
February 15, 2019 - New AI-driven platform analyze how pathogens infect human cells
February 15, 2019 - Increased activity of EHMT2 gene deficient neurons could cause autism in humans
February 15, 2019 - Recurring UTIs may mask symptoms of bladder or kidney cancer
February 15, 2019 - Researchers conduct extensive comparison of drugs used in treating neuroendocrine tumors
February 15, 2019 - Depression prevention for pregnant women and new mothers – new recommendations
February 15, 2019 - AHA News: Are There Health Benefits From Chocolate?
February 15, 2019 - The involvement of the gut in Parkinson’s disease: hype or hope?
February 15, 2019 - New PET imaging agent may help measure efficacy or failure of hormone therapy for breast cancer
February 15, 2019 - Preventing infections could help combat antimicrobial resistance
February 15, 2019 - Study investigates the role of estrogen in controlling glucose homeostasis
February 15, 2019 - Exposure to chemical in weedkiller Roundup raises risk of some cancers, study finds
February 15, 2019 - Smoking and drinking during pregnancy – stigma drives women to secrecy
February 15, 2019 - Low FODMAP diet reduces stomach issues caused by exercise
February 15, 2019 - Novel approach uses small amounts of tissue to quantify PD-L1 expression levels in tumors
February 15, 2019 - Breast pumps could be transmitting asthma-causing bacteria in babies, finds study
February 15, 2019 - The Pistoia Alliance Launches Next Phase of Blockchain Project to Develop Life Science R&D Use Cases
February 15, 2019 - The search for environmental causes of Parkinson’s disease moves forward
February 15, 2019 - Women scientists inhibited by funding methods that favor men, researchers say
February 14, 2019 - Few primary care physicians lack enough knowledge of cancer treatment options
February 14, 2019 - Prime real estate is determined by previous owner in the squirrel world
February 14, 2019 - Discovery of a ‘master switch’ within the immune system
February 14, 2019 - Health officers with surgical training are a safe alternative for performing C-sections
Mutation that causes autism and intellectual disability makes brain less flexible

Mutation that causes autism and intellectual disability makes brain less flexible

image_pdfDownload PDFimage_print
Mice help scientists uncover the mechanisms behind autism spectrum disorders and intellectual disability. Credit: IST Austria/Isabel Chew

About 1 percent of patients diagnosed with autism spectrum disorder and intellectual disability have a mutation in a gene called SETD5. Scientists have now discovered what happens on a molecular level when the gene is mutated in mice, and how this changes the mice’s behavior. This is an important step towards understanding how mutations in the SETD5 gene may cause cognitive changes in affected patients. The study was led by Gaia Novarino, Professor at IST Austria, and Kyung-Min Noh, Group leader at the European Molecular Biology Laboratory in Heidelberg, Germany; Elena Deliu, Niccolo Arecco, Jasmin Morandell and Christoph Dotter share first authorship. The results, which suggest that the brains of mice with a SETD5 mutation may be less flexible, are published today in Nature Neuroscience.

In a previous study published in 2014, Gaia Novarino, in collaboration with a group at Bonn University, identified mutations in the gene SETD5 as a relatively frequent cause of intellectual disability and autism. Among patients who are diagnosed with intellectual disability and/or autism spectrum disorder that can be traced to a gene mutation, 1% has a mutation in the gene SETD5. Before the follow-up study published now, however, it was not known what SETD5 does, says Novarino: “This was the motivation for our work. Knowing nothing about this gene, we wanted to find out what its product does.”

The researchers set about characterizing what the SETD5 gene product does on a molecular level and link this to how behavior changes when SETD5 is mutated. This endeavor was not about understanding mouse biology though, Gaia Novarino clarifies. “We want to know what happens in patients who have a mutation in SETD5. To be able to understand this, we made mice that have the same genetic defect as seen in humans.”

For their studies, the researchers characterized what happens in mice which carry one mutated copy of SETD5 and one intact copy of the gene. They found that in the mouse embryo, SETD5 is important for regulating gene transcription, the process by which the blueprint of DNA is turned into a set of instructions for making proteins. In early development, SETD5 plays a role in the specification of tissues, this is the reason why developmental defects are seen when SETD5 is mutated.

Later on in life, SETD5 regulates gene transcription in dynamic processes when signals are integrated, for example to form memories or during learning. When mice with SETD5 mutation are set a learning challenge, the dynamics of gene transcription is different from that in mice without the mutation.

The researchers hypothesize that mice with a SETD5 mutation have a more inflexible brain. SETD5 mice were found to make memories that are too strong and not easily overwritten. “In the brain, balance and precise response are important. The SETD5 mice make more stable memories, which could make the brain inflexible. Because the brain is less flexible, they cannot easily make new memories or adapt to new situations”, Gaia Novarino explains.

The study authors also found that SETD5 cooperates with other proteins to regulate gene expression during learning and memory formation. Several of these associated genes, when mutated, also lead to intellectual disability and/or autism spectrum disorder in patients, says Kyung-Min Noh. “We have found a cluster of genes that are all related to these disorders.”

Understanding the molecular function of SETD5 and linking it to mouse behavior was an important step towards helping patients. “When we look at the brain of these mice, the structure hasn’t changed. So there is no structural barrier that would give a reason why treating patients with SETD5 mutations wouldn’t be possible”, Novarino explains, “This gives us hope that eventually, we will understand how to treat the cognitive issues of patients with SETD5 mutations. The extent to which the condition is treatable will be seen. We have hope.”


Explore further:
New form of autism found

More information:
Elena Deliu et al, Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition, Nature Neuroscience (2018). DOI: 10.1038/s41593-018-0266-2

Journal reference:
Nature Neuroscience

Provided by:
Institute of Science and Technology Austria

Tagged with:

About author

Related Articles