Gene-targeting technologies for the study of neurological disorders |
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Authors: | Vassilios Beglopoulos Jie Shen |
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Institution: | (1) Center for Neurologic Diseases, Brigham and Women’s Hospital, Program in Neuroscience, Harvard Medical School, 02115 Boston, MA |
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Abstract: | Studies using genetic manipulations have proven invaluable in the research of neurological disorders. In the forefront of
these approaches is the knockout technology that engineers a targeted gene mutation in mice resulting in inactivation of gene
expression. In many cases, important roles of a particular gene in embryonic development have precluded the in vivo study
of its function in the adult brain, which is usually the most relevant experimental context for the study of neurological
disorders. The conditional knockout technology has provided a tool to overcome this restriction and has been used successfully
to generate viable mouse models with gene inactivation patterns in certain regions or cell types of the postnatal brain. This
review first describes the methodology of gene targeting in mice, detailing the aspects of designing a targeting vector, introducing
it into embryonic stem cells in culture and screening for correct recombination events, and generating chimeric and null mutant
mice from the positive clones. It then discusses the special issues and considerations for the generation of conditional knock-out
mice, including a section about approaches for inducible gene inactivation in the brain and some of their applications. An
overview of gene-targeted mouse models that have been used in the study of several neurological disorders, including Alzheimer’s
disease, Parkinson’s disease, Huntington’s disease, seizure disorders, and schizophrenia, is also presented. The importance
of the results obtained by these models for the understanding of the pathogenic mechanism underlying the disorders is discussed. |
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Keywords: | Mouse knockout conditional inducible genetics disease model Alzheimer’ s disease Parkinson’ s disease Huntington’ s disease seizure schizophrenia |
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