Neuroscientists have now shed some light on how a single gene can play a role in more than one disease. In a study appearing in the journal Neuron, they revealed that two different mutations of the Shank3 gene produce some distinct molecular and behavioral effects in mice.
The protein encoded by Shank3 is found in synapses -- the junctions between neurons that allow them to communicate with each other. Shank3 is a scaffold protein, meaning it helps to organize hundreds of other proteins clustered on the postsynaptic cell membrane, which are required to coordinate the cell's response to signals from the presynaptic cell.
Scientists engineered mice with each of the two mutations: The schizophrenia-related mutation results in a truncated version of the Shank3 protein, while the autism-linked mutation leads to a total loss of the Shank3 protein.
Behaviorally, the mice shared many defects, including strong anxiety. However, the mice with the autism mutation had very strong compulsive behavior, manifested by excessive grooming, which was rarely seen in mice with the schizophrenia mutation.
In the mice with the schizophrenia mutation, the researchers saw a type of behavior known as social dominance. These mice trimmed the whiskers and facial hair of the genetically normal mice sharing their cages, to an extreme extent.
By activating the mutations in different parts of the brain and at different stages of development, the researchers found that the two mutations affected brain circuits in different ways. The autism mutation exerted its effects early in development, primarily in a part of the brain known as the striatum, which is involved in coordinating motor planning, motivation, and habitual behavior. The author believes that disruption of synapses in the striatum contributes to the compulsive behavior seen in those mice.
In mice carrying the schizophrenia-associated mutation, early development was normal, suggesting that truncated Shank3 can adequately fill in for the normal version during this stage. However, later in life, the truncated version of Shank3 interfered with synaptic functions and connections in the brain's cortex, where executive functions such as thought and planning occur. This suggests that different segments of the protein -- including the stretch that is missing in the schizophrenia-linked mutation -- may be crucial for different roles, author says.
Although only a small percentage of autism patients have mutations in Shank3, many other variant synaptic proteins have been associated with the disorder. Future studies should help to reveal more about the role of the many genes and mutations that contribute to autism and other disorders, author says. Shank3 alone has at least 40 identified mutations, author says.
http://news.mit.edu/2015/shank3-gene-autism-schizophrenia-1210
Edited
Latest News
Psychosocial experiences ar…
By newseditor
Posted 25 Jun
How a microbe and a prebiot…
By newseditor
Posted 24 Jun
Slowing inflammation may bo…
By newseditor
Posted 24 Jun
Cellular senescence in norm…
By newseditor
Posted 24 Jun
Neuronal communication capt…
By newseditor
Posted 24 Jun
Other Top Stories
Restoring glucose production by glucagon through calcium mediated i…
Read more
The glial role in feeling satiety after a meal
Read more
Brain aging could be detected early and reversed by low carb diet
Read more
Are bacteria involved in the development of type 2 diabetes?
Read more
Protein controls fat metabolism
Read more
Protocols
Deciphering spatial domains…
By newseditor
Posted 23 Jun
High-throughput volumetric…
By newseditor
Posted 21 Jun
Bioengineered human colon o…
By newseditor
Posted 14 Jun
Development of an efficient…
By newseditor
Posted 12 Jun
A co-culture system of macr…
By newseditor
Posted 10 Jun
Publications
Nicotinamide metabolism fac…
By newseditor
Posted 26 Jun
Tonic type 2 immunity is a…
By newseditor
Posted 26 Jun
An unexpected role for the…
By newseditor
Posted 25 Jun
Coordinated action of a gut…
By newseditor
Posted 25 Jun
Safety of non-replicative a…
By newseditor
Posted 25 Jun
Presentations
Myelin plasticity in the ve…
By newseditor
Posted 10 Jun
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar