CAS scientists make autism advance using monkey model

August 18, 2017

Autism is a common neurodevelopmental disorder characterized by impaired social communication, and restricted and repetitive behavior or interests. The reported prevalence of autism has been rising worldwide. Due to the application of large-scale exome sequencing in recent years, hundreds of novel autism-associated genes have been identified.

Mutations in SHANK3 remain one of the best characterized and replicated genetic defects associated with autism in humans. Genetically modified Shank3 mutant mice have served as valuable tools to dissect the pathophysiology of SHANK3 as related to autism. However, the significant evolutionary differences between the mouse and human brain and associated behaviors pose many challenges to assessing the translational value of mouse models in relation to humans, and highlight the need to develop non-human primate models.

Recently, researchers from Dr. ZHANG Yongqing's group at the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences (CAS) found neurodevelopmental abnormality in a SHANK3-deficient non-human primate for the first time.

Using CRISPR/Cas9 to target the SHANK3 gene in the embryos of cynomolgus monkeys, the researchers successfully generated three mutant monkey offspring with various deleterious mutations in the SHANK3 gene. They analyzed the targeted mutations in various tissues from the three animals, as well as various brain regions of the deceased animals by immunochemical analysis.

Complete SHANK3 deficiency resulted in a significant reduction in postsynaptic proteins such as GluN2B, PSD95, mGluR5 and increased cytosolic localization of Homer1b/c. The number of mature neurons was markedly reduced but activated astrocytes were increased in the prefrontal cortex in the SHANK3-deficient brain. The neuropathology caused by the complete loss of SHANK3 in the monkey brain is remarkably distinct from findings reported from Shank3 knockout mice.

These findings indicate that SHANK3 is essential for the early development of primate brains. Understanding the novel role of SHANK3 in early brain development is critical to the autism field.

This work is a product of substantial collaboration between teams led by Drs. LI Xiaojiang (CAS), JIANG Yonghui (Duke University Medical Center), LU Youming (Huazhong University of Science and Technology), and Yuanxi Biotech Inc., Guangzhou. The research, entitled "Altered neurogenesis and disrupted expression of synaptic proteins in prefrontal cortex of SHANK3-deficient non-human primate," has been published in advance online in Cell Research (doi:10.1038/cr.2017.95).
-end-
This project was supported by the Ministry of Science and Technology of China, the Chinese Academy of Sciences, and the National Natural Science Foundation of China.

Chinese Academy of Sciences Headquarters

Related Autism Articles from Brightsurf:

Autism-cholesterol link
Study identifies genetic link between cholesterol alterations and autism.

National Autism Indicators Report: the connection between autism and financial hardship
A.J. Drexel Autism Institute released the 2020 National Autism Indicators Report highlighting the financial challenges facing households of children with autism spectrum disorder (ASD), including higher levels of poverty, material hardship and medical expenses.

Autism risk estimated at 3 to 5% for children whose parents have a sibling with autism
Roughly 3 to 5% of children with an aunt or uncle with autism spectrum disorder (ASD) can also be expected to have ASD, compared to about 1.5% of children in the general population, according to a study funded by the National Institutes of Health.

Adulthood with autism
The independence that comes with growing up can be scary for any teenager, but for young adults with autism spectrum disorder and their caregivers, the transition from adolescence to adulthood can seem particularly daunting.

Brain protein mutation from child with autism causes autism-like behavioral change in mice
A de novo gene mutation that encodes a brain protein in a child with autism has been placed into the brains of mice.

Autism and theory of mind
Theory of mind, or the ability to represent other people's minds as distinct from one's own, can be difficult for people with autism.

Potential biomarker for autism
A study of young children with autism spectrum disorder published in JNeurosci reveals altered brain waves compared to typically developing children during a motor control task.

Autism often associated with multiple new mutations
Most autism cases are in families with no previous history of the disorder.

State laws requiring autism coverage by private insurers led to increases in autism care
A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health has found that the enactment of state laws mandating coverage of autism spectrum disorder (ASD) was followed by sizable increases in insurer-covered ASD care and associated spending.

Autism's gender patterns
Having one child with autism is a well-known risk factor for having another one with the same disorder, but whether and how a sibling's gender influences this risk has remained largely unknown.

Read More: Autism News and Autism Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.