People are still not sure what causes autism, which is a type of brain disorder. Scientists use mice to investigate the condition in more detail. BTBR/J mice are the most popular ones used for this purpose.
Scientists from all around the world have recently made new findings about when autism starts in mice. Kobe University’s Professor Toru Takumi and Researcher Chia-wen Lin were part of this international research team.
Scientists conducted experiments and tests with two diverse species of mice, BTBR/J and BTBR/R. They discovered that an increase in the virus activation of a fetus increases their chance of developing autism. In addition, they also found out that even though the BTBR/R type displays autistic-like behaviors, its learning capabilities remain unchanged, thus making it a better substitute to study autism than the commonly used BTBR/J strain.
Scientists are working on researching autism and related disorders more so that they can create better ways to diagnose them and more effective treatments. On March 7, 2023, the results of this research were printed in the journal Molecular Psychiatry.
Brain Connection Not Functioning Properly in BTBR/J Mice, but Retrovirus Genes Discovered in Both Types
Researchers used MRI to study two types of mouse models that are commonly used for autism research: BTBR/J and its subspecies BTBR/R. They discovered that the connection between the left and right side of the brain, called corpus callosum, was not working properly in the BTBR/J mice but it was normal in the BTBR/R mice. Additionally, genome and transcription analysis revealed that these rodents had increased levels of retrovirus genes inside their bodies.
Experts looked at single cells from different types of mice, BTBR/J and BTBR/R. They noticed changes in the activity of certain genes that can cause stress. Even though these two types of mouse come from the same family, they act differently when it comes to spatial learning and other behaviours.
Unraveling the Mysteries of Autism
We all need to take responsibility for our lives and make sure that we do the right things to achieve our goals. It’s important that we think about the consequences of our decisions, stay positive and believe in ourselves. We should be open-minded and willing to take risks because only then can we really experience growth and success.
Autism (also known as autism spectrum disorder) is a brain illness that more and more people are being diagnosed with. It’s thought to be caused by things like changes to diagnosis rules, or fathers who are older when they have kids. Autism is tied to genes – meaning it can be the result of issues like DNA copying that doesn’t go right. Scientists use animals, especially mice, in tests to figure out how autism works. One type of mouse used for this research has been called BTBR/J – and these seem to display signs of autism-like behavior (acting similar to people with autism). Experiments on these mice also reveal things like their corpus callosum (the part of their brain that connects the left and right halves) not working properly, and odd ways in which their immune system reacts. But we’re still not clear about why these particular mice act the way they do.
This study tried to figure out why people with autistic-like behaviour have these issues by comparing the BTBR/J and its type, BTBR/R.
Differences in Behavior and Brain Structures of BTBR/J and BTBR/R Mice Revealed by MRI Scans
Scientists performed MRI scans on two kinds of mice – BTBR/J and BTBR/R – to check if there were any differences in different parts of their brains. The results showed that there were various differences in the 33 regions they looked at, with a very interesting one being that the corpus callosum — which is part of the brain’s wiring system — was working normally in BTBR/R mice, but not in BTBR/J mice (see Figure 1).
The group of researchers used a method called “array CGH” to compare how different the copy numbers were between two kinds of mice; BTBR/R and B6. They discovered that in BTBR/R mice, there was a much higher amount of retroviruses than in B6 mice. To make sure these viruses weren’t just dormant but active too, they did another test- called qRT-PCR- and figured out that yes, the viruses were indeed active inside BTBR/R. But interestingly even though both types of mice have similar virus types (called LINE ERV), no such viral activation happened for B6 mice which indicated that only BTBR had this kind of activity going on.
Researchers studied samples from the tissue of special mice called BTBR on their AGM and yolk sac. They found that there were changes in a group of genes which are linked to ERV, this means ERV is active in BTBR mice (Figure 3).
After examining the behavior of BTBR/J and BTBR/R mice, researchers found that BTBR/R were less anxious and had better communication skills than their counterparts. They also showed more self-grooming behaviors, like burying more marbles in a marble test – an experiment used to understand repetitive behavior usually seen in people with autism. When put alongside each other in a 3-chamber social interaction test,BTBR/R did worse, showing that they are more symptomatic than BTBR/J. Lastly, when given a spatial learning challenge in a Barnes maze game, BTBR/J didn’t do as well as B6 mice (normal mice), whereas BTBR/R performed just as well as them.
Our study showed that viruses can cause the number of BTBR mouse copies to go up; this leads to the different behaviors and brains seen between the BTBR/J and BTBR/R mice (shown in Figure 5).
Exploring the Role of Endogenous Retroviruses in Autism Spectrum Disorder
Studies have shown that young minds are more prone to creative thinking than older ones. This means that the ideas and solutions kids come up with can be innovative and different from what we usually expect. However, due to their lack of experience, it’s important for adults to guide them in the right direction. This will help their ideas reach their highest potential!
Researchers usually use BTBR/J mice as a model of autism. However, our study shows that the other type of BTBR/R mice can also be helpful because they show some behaviors similar to those seen in people with autism while not having trouble learning things. Our results tell us there may be new ways to treat autism by stopping something called ERV activation. Finally, it’s important to classify different types of autism based on how they start so that we can find more treatments for them.
This article, written by Chia-Wen Lin, Jacob Ellegood, Kota Tamada, Ikuo Miura, Mikiko Konda, Kozue Takeshita, Koji Atarashi, Jason P. Lerch, Shigeharu Wakana, Thomas J. McHugh and Toru Takumi talks about how ENDOGENOUS RETROVIRUSES are connected to Autism Spectrum Disorder (ASD). It explains how these retroviruses have an importance in the evolvement of ASD and it also looks at how they can hijack transcription machinery during development. This study was published on 7th March 2023 in Molecular Psychiatry with a DOI code of 10.1038/s41380-023-01999-z.
Unlock Your Potential and Explore the World of Autism!
Autism is a complex disorder caused by both genetic and environmental factors. Even though sometimes the cause can’t be determined, it’s known as ‘Idiopathic Autism’. Endogenous retrovirus (RNA virus with reverse transcription) comprise 8% of the human genome and Neurodevelopmental disorder, previously called developmental disorder, is a problem related to the brain. There are two lines of mice known as BTBR/J and BTBR/R that imitate autism behavior. MRI (Magnetic Resonance Imaging) is used to take pictures of our organs, like the Corpus callosum which connects left and right brain hemispheres together. Single-cell RNA-seq method involves studying all mRNA present in individual cells while Copy number variation looks for duplications or deletions of genomic DNA on chromosomes. Array CGH method detects any chromosomes abnormality high-resolutionly. AGM is an hematopoietic region found inside fetus and Yolk sac helps with development of early stage fetus too. To gauge sociability between mice in an experiment, the 3-chamber social interaction test is taken into consideration!
