Understanding the Function of SIGMAR1 Gene in Neurons Using TALEN-mediated Mutagenesis

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2015-04-14
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Mullally, Madelyn
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Amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, is a neurodegenerative disease caused by the death of motor neurons in the central nervous system. The death of these nerve cells leads to the degeneration of the patient’s muscle cells, resulting in paralysis and eventually death. Because the majority of ALS cases are sporadic, there is not a clear understanding of the molecular and genetic mechanisms that lead to the death of the motor neurons. Superoxide dismutase (SOD1) is one gene that has been implicated in ALS, but there are also a large number of genes that are linked to ALS but have not been studied in depth. Sigma non-opioid intracellular receptor 1 (SIGMAR1) is one gene that has been found to have a connection to different forms of ALS, including juvenile ALS, but the relationship between the two is not understood. To gain a better understanding into SIGMAR1’s role in the development and death of motor neurons, we are using Tal-effector nuclease (TALEN) mediated mutagenesis to create SIGMAR1 mutant zebrafish. Once created, these fish will hopefully provide insights into the function of SIGMAR1 and allow us to create a new model of nerve cell degeneration.

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