Abstract
The diagnosis of schizophrenia rests on clinical criteria that cannot be assessed in animal models. Together with absence of a clear underlying pathology and understanding of what causes schizophrenia, this has hindered development of informative animal models. However, recent large-scale genomic studies have identified copy number variants (CNVs) that confer high risk of schizophrenia and have opened a new avenue for generation of relevant animal models. Eight recurrent CNVs have reproducibly been shown to increase the risk of schizophrenia by severalfold: 22q11.2(del), 15q13.3(del), 1q21(del), 1q21(dup), NRXN1(del), 3q29(del), 7q11.23(dup), and 16p11.2(dup). Five of these CNVs have been modeled in animals, mainly mice, but also rats, flies, and zebrafish, and have been shown to recapitulate behavioral and electrophysiological aspects of schizophrenia. Here, we provide an overview of the schizophrenia-related phenotypes found in animal models of schizophrenia high-risk CNVs. We also discuss strengths and limitations of the CNV models, and how they can advance our biological understanding of mechanisms that can lead to schizophrenia and can be used to develop new and better treatments for schizophrenia.
Citations
May 30, 2019·Molecular Psychiatry·Zhonghua HuMing Li
May 21, 2020·Disease Models & Mechanisms·Philip D Campbell, Michael Granato
May 1, 2020·Genome Medicine·Elliott Rees, Michael J Owen
Sep 23, 2020·Journal of Human Genetics·Masahiro NakatochiNorio Ozaki
Nov 11, 2019·Molecular Psychiatry·Aaron GordonDaniel H Geschwind
Feb 19, 2020·Translational Psychiatry·Ryo SaitoAtsu Aiba
Jan 21, 2021·Expert Opinion on Drug Discovery·Marinos G SotiropoulosNikolaos Kokras
Mar 23, 2021·Current Opinion in Genetics & Development·Elliott Rees, George Kirov
Apr 17, 2021·Molecular Psychiatry·Mitsuteru NakamuraNoboru Hiroi
May 7, 2021·Current Opinion in Genetics & Development·Steven E Hyman
Jun 3, 2021·International Journal of Molecular Sciences·Joy Yoon, Yingwei Mao
Jun 23, 2021·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Pengjie WangJie Ma
Dec 11, 2021·Genes, Brain, and Behavior·Arianna BenedettiFrancesco Papaleo