Zebrafish as a tool to study schizophrenia-associated copy number variants
Schizophrenia remains one of the most debilitating human neurodevelopmental disorders, with few effective treatments and striking consequences felt by individuals, communities and society as a whole. As such, there remains a critical need for further investigation into the mechanistic underpinnings...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2020-04-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/13/4/dmm043877 |
| _version_ | 1818255873713111040 |
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| author | Philip D. Campbell Michael Granato |
| author_facet | Philip D. Campbell Michael Granato |
| author_sort | Philip D. Campbell |
| collection | DOAJ |
| description | Schizophrenia remains one of the most debilitating human neurodevelopmental disorders, with few effective treatments and striking consequences felt by individuals, communities and society as a whole. As such, there remains a critical need for further investigation into the mechanistic underpinnings of schizophrenia so that novel therapeutic targets can be identified. Because schizophrenia is a highly heritable disorder, genetic risk factors remain an attractive avenue for this research. Given their clear molecular genetic consequences, recurrent microdeletions and duplications, or copy number variants (CNVs), represent one of the most tractable genetic entry points to elucidating these mechanisms. To date, eight CNVs have been shown to significantly increase the risk of schizophrenia. Although rodent models of these CNVs that exhibit behavioral phenotypes have been generated, the underlying molecular mechanisms remain largely elusive. Over the past decades, the zebrafish has emerged as a powerful vertebrate model that has led to fundamental discoveries in developmental neurobiology and behavioral genetics. Here, we review the attributes that make zebrafish exceptionally well suited to investigating individual and combinatorial gene contributions to CNV-mediated brain dysfunction in schizophrenia. With highly conserved genetics and neural substrates, an ever-expanding molecular genetic and imaging toolkit, and ability to perform high-throughput and high-content genetic and pharmacologic screens, zebrafish is poised to generate deep insights into the molecular genetic mechanisms of schizophrenia-associated neurodevelopmental and behavioral deficits, and to facilitate the identification of therapeutic targets. |
| first_indexed | 2024-12-12T17:18:47Z |
| format | Article |
| id | doaj.art-8cf0fcad762b43f29f75225bcf40c0d7 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-12T17:18:47Z |
| publishDate | 2020-04-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-8cf0fcad762b43f29f75225bcf40c0d72022-12-22T00:17:43ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112020-04-0113410.1242/dmm.043877043877Zebrafish as a tool to study schizophrenia-associated copy number variantsPhilip D. Campbell0Michael Granato1 Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Schizophrenia remains one of the most debilitating human neurodevelopmental disorders, with few effective treatments and striking consequences felt by individuals, communities and society as a whole. As such, there remains a critical need for further investigation into the mechanistic underpinnings of schizophrenia so that novel therapeutic targets can be identified. Because schizophrenia is a highly heritable disorder, genetic risk factors remain an attractive avenue for this research. Given their clear molecular genetic consequences, recurrent microdeletions and duplications, or copy number variants (CNVs), represent one of the most tractable genetic entry points to elucidating these mechanisms. To date, eight CNVs have been shown to significantly increase the risk of schizophrenia. Although rodent models of these CNVs that exhibit behavioral phenotypes have been generated, the underlying molecular mechanisms remain largely elusive. Over the past decades, the zebrafish has emerged as a powerful vertebrate model that has led to fundamental discoveries in developmental neurobiology and behavioral genetics. Here, we review the attributes that make zebrafish exceptionally well suited to investigating individual and combinatorial gene contributions to CNV-mediated brain dysfunction in schizophrenia. With highly conserved genetics and neural substrates, an ever-expanding molecular genetic and imaging toolkit, and ability to perform high-throughput and high-content genetic and pharmacologic screens, zebrafish is poised to generate deep insights into the molecular genetic mechanisms of schizophrenia-associated neurodevelopmental and behavioral deficits, and to facilitate the identification of therapeutic targets.http://dmm.biologists.org/content/13/4/dmm043877zebrafishschizophreniaattention-deficit/hyperactivity disorderadhdautism spectrum disordersasdcopy number variantgeneticspsychiatrybehaviorintellectual disabilitiesid, developmental delay, dd |
| spellingShingle | Philip D. Campbell Michael Granato Zebrafish as a tool to study schizophrenia-associated copy number variants Disease Models & Mechanisms zebrafish schizophrenia attention-deficit/hyperactivity disorder adhd autism spectrum disorders asd copy number variant genetics psychiatry behavior intellectual disabilities id, developmental delay, dd |
| title | Zebrafish as a tool to study schizophrenia-associated copy number variants |
| title_full | Zebrafish as a tool to study schizophrenia-associated copy number variants |
| title_fullStr | Zebrafish as a tool to study schizophrenia-associated copy number variants |
| title_full_unstemmed | Zebrafish as a tool to study schizophrenia-associated copy number variants |
| title_short | Zebrafish as a tool to study schizophrenia-associated copy number variants |
| title_sort | zebrafish as a tool to study schizophrenia associated copy number variants |
| topic | zebrafish schizophrenia attention-deficit/hyperactivity disorder adhd autism spectrum disorders asd copy number variant genetics psychiatry behavior intellectual disabilities id, developmental delay, dd |
| url | http://dmm.biologists.org/content/13/4/dmm043877 |
| work_keys_str_mv | AT philipdcampbell zebrafishasatooltostudyschizophreniaassociatedcopynumbervariants AT michaelgranato zebrafishasatooltostudyschizophreniaassociatedcopynumbervariants |