SchizophrenicWords: DISC1 Gene
-Transgenic Mice Provide New Insight into Schizophrenia-
Akira Sawa has been messing with mice, and now they’re schizophrenic. Recently, the Johns Hopkins neuroscientist elimated expression of the DISC-1 gene in rodents, and he showed this to delay neuronal development. Sawa’s population of transgenic mice exhibits the same delayed neuronal migration seen in another group: schizophrenic humans.
Sawa hopes to use his transgenic models to better understand development of schizophrenia – a disease with no known cure. “There are no clear cut biological markers for the disease,” he explained, and as such, both environmental and genetic factors have been implicated in causing it.
While some researchers point to the delayed onset of schizophrenia (manifest at ages 15 to 30) as a sign that environmental factors are to blame, Sawa joins those who ascribe a larger role to genetic predisposition. “There are several candidate genes for schizophrenic susceptibility,” he said, and though he acknowledges that environmental factors (psychological stress in childhood, viral infection in the womb) have a role in schizophrenic development, Sawa’s take is that the disorder actually starts before birth, as the brain develops.
To prove this, Sawa sought to link genetics to poor neuronal migration- a hallmark of schizophrenia. In his study, he focused on manipulation of one gene in the candidate list: DISC-1. Why this gene? “There are a lot of false positives in these studies,” Sawa explained, in reference to the list of genes implicated in the disorder, and “90% of these are junk,” he said. However, Sawa selected DISC-1 because, unlike the other candidate genes, it was not a known gene with a known function. Additionally, “only DISC-1 has a clear-disease associated mutation.”
Furthermore, previous studies link a truncated DISC-1 gene to familial history of schizophrenia. In his experiment, Sawa had no power to truncate DISC-1, but he was able to observe what happened when something went wrong with the gene by eliminating its expression all together. To do this, he introduced Ribonucleic Acid Interference (RNAi) into mouse embryos. RNAi targets a specific gene and silences its expression by preventing protein synthesis. Sawa used electric current to open channels and insert the RNAi targetting DISC-1 into the heads of mice developing in the womb. At this stage, neuronal abnormalities could be observed in the mouse brains.
In normal brain development, neurons migrate from inside the chambers of the brain to its outer cortex at a certain rate. This process was significantly delayed in the transgenic mice, however, reflecting poor neuronal migration. This is what Sawa had hoped to see. A biological marker had been established in DISC-1.
Sawa’s mice models provide means for pharamaceutical companies to test new therapies, based on biological markers. Sawa stipulates that this just the beginning of understanding schizophrenia, though; more biomarkers must be found in people before schizophrenia can be cured. Sawa explained that with stem cells harvested from humans, more biomarkers will be able to be pinpointed. It’s good to know that these markers can be tested in the the minds of mice so that someday soon, the minds of men will be less plagued by disease. Sawa’s messing with mice may yet yield a masterpiece in the treatment of schizophrenia.
.MGW.
Akira Sawa has been messing with mice, and now they’re schizophrenic. Recently, the Johns Hopkins neuroscientist elimated expression of the DISC-1 gene in rodents, and he showed this to delay neuronal development. Sawa’s population of transgenic mice exhibits the same delayed neuronal migration seen in another group: schizophrenic humans.
Sawa hopes to use his transgenic models to better understand development of schizophrenia – a disease with no known cure. “There are no clear cut biological markers for the disease,” he explained, and as such, both environmental and genetic factors have been implicated in causing it.
While some researchers point to the delayed onset of schizophrenia (manifest at ages 15 to 30) as a sign that environmental factors are to blame, Sawa joins those who ascribe a larger role to genetic predisposition. “There are several candidate genes for schizophrenic susceptibility,” he said, and though he acknowledges that environmental factors (psychological stress in childhood, viral infection in the womb) have a role in schizophrenic development, Sawa’s take is that the disorder actually starts before birth, as the brain develops.
To prove this, Sawa sought to link genetics to poor neuronal migration- a hallmark of schizophrenia. In his study, he focused on manipulation of one gene in the candidate list: DISC-1. Why this gene? “There are a lot of false positives in these studies,” Sawa explained, in reference to the list of genes implicated in the disorder, and “90% of these are junk,” he said. However, Sawa selected DISC-1 because, unlike the other candidate genes, it was not a known gene with a known function. Additionally, “only DISC-1 has a clear-disease associated mutation.”
Furthermore, previous studies link a truncated DISC-1 gene to familial history of schizophrenia. In his experiment, Sawa had no power to truncate DISC-1, but he was able to observe what happened when something went wrong with the gene by eliminating its expression all together. To do this, he introduced Ribonucleic Acid Interference (RNAi) into mouse embryos. RNAi targets a specific gene and silences its expression by preventing protein synthesis. Sawa used electric current to open channels and insert the RNAi targetting DISC-1 into the heads of mice developing in the womb. At this stage, neuronal abnormalities could be observed in the mouse brains.
In normal brain development, neurons migrate from inside the chambers of the brain to its outer cortex at a certain rate. This process was significantly delayed in the transgenic mice, however, reflecting poor neuronal migration. This is what Sawa had hoped to see. A biological marker had been established in DISC-1.
Sawa’s mice models provide means for pharamaceutical companies to test new therapies, based on biological markers. Sawa stipulates that this just the beginning of understanding schizophrenia, though; more biomarkers must be found in people before schizophrenia can be cured. Sawa explained that with stem cells harvested from humans, more biomarkers will be able to be pinpointed. It’s good to know that these markers can be tested in the the minds of mice so that someday soon, the minds of men will be less plagued by disease. Sawa’s messing with mice may yet yield a masterpiece in the treatment of schizophrenia.
.MGW.
posted by Meagan G at
9:27 PM
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