12.07>> Autism    
Genetic Link of Autism  

The black widow spider is common to much of North America. It is also responsible for more human deaths than any other spider. Black widow spider venom contains a potent neurotoxin, a chemical that affects how neurons in the central nervous system work.

To understand how this venom works, we first must understand how neurons function. Neurons are separated from each other by a tiny space called the synapse, as indicated in the schematic below, which shows a portion of one neuron, the synapse, and a portion of the next neuron:

To transmit a signal, one neuron, called the presynaptic neuron, will send chemical neurotransmitters across the synapse to receptors on the next neuron, which is called the postsynaptic neuron. That neuron will then release neurotransmitters to the next neuron and the process continues until a response occurs, such as moving an arm or leg, or sensing pain. (For more complete details, see #4 under To Learn More at the end of this story). You can also check out this short YouTube animation.

The specific neurotoxin made by the black widow spider is called neurexin. It is normally found in very small amounts in the central nervous system, which is why the body has receptors to it. Neurexin’s job is to tell neurons to stop firing, so it is known as an inhibitory neurotransmitter. When the spider injects this venom into an organism, the excess amount of neurexin inhibits (stops) all neuron function, causing paralysis or death.

Interestingly, the chemical used by the black widow spider to kill its prey has a role in autism. Autism is a group of diseases all characterized by impaired social skills. It is believed to be caused by a combination of genetic and environmental factors. Dr. Thomas Südhof, at the University of Texas Southwestern Medical Center in Dallas, Texas, studies how genes affect disease. In particular, Dr. Südhof studies how genes affect the transmission of signals across synapses in the central nervous system.

Dr. Südhof recently created the first true mouse model of autism by replicating the genetic mutation of two identical twin brothers. Both brothers had the same mutation, but, for some reason, developed different forms of autism. One brother had autism and the other had a milder form of the disease called Asperger’s Syndrome.

To study this mutation, Dr. Südof bred mice with this mutation through a process called “knock-in” or inserting a gene into an animal. The mutation was in a protein that encodes the neurotransmitter, neuroligin. Neuroligin is related to neurexin used by the black widow spider. Neuroligin is, in fact, the receptor onto which neurexin binds on the “other side” (postsynaptic) of the synapse. Neuroligin was mutated in such a way that receptor binding occurred, but the process of transmitting a signal to the next neuron was slowed down.

The mouse models with mutated neuroligin exhibited some of the same characteristics of autistic humans. Mice are very social animals that enjoy the company of other mice. When a normal mouse is put into a cage with another mouse, the two mice will usually interact. When a mutated mouse was put in a cage with another mouse, however, it stayed by itself and did not seek out other mice. This is characteristic of the social impairment of autistic humans.

The mutated mice also showed increased intelligence as do some autistic people. To test for heightened intelligence, Dr. Südhof used the Richard Morris Water Maze Test. In this test, a mouse is placed into a tank of water. There is a hidden platform nearby so the mouse can get out of the water. The test measures the amount of time it takes for a given mouse to find the platform. Dr. Südhof found that mice with this mutation consistently found the platform quicker than their control counterparts.

Dr. Südhof’s model is the first mouse model of autism that has focused on the genetic components of the disease linking a mutation with the biological reaction affected by the mutation. Using this model, he soon hopes to understand the biology of autism, which may lead to better care, treatment, and, eventually, may even be able to prevent this type of autism.

Dr. Südhof is a Professor of Molecular Genetics at the University of Texas Southwestern Medical Center and a researcher at the Howard Hughes Medical Institute. His research focuses on the pathways that control synaptic action in the central nervous system and how certain mutations in relevant genes affect these pathways.


Dr. Thomas Südhof

Neurons and How They Work
Neural Process Animation
From thinkquest.org
Student Worksheet
December 2007
Teacher Guidance
December 2007

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What A Year! is a project of the Massachusetts Society for Medical Research.

And it is funded by a grant from The William Townsend Porter Foundation.


To Learn More

For Information On Autism:

Rebecca Kranz with Andrea Gwosdow, Ph.D.



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