Making a mouse model for schizophrenia:Using the mouse to model the schizophreniasusceptibility gene ZNF804A
Year: 2012
Type: dissertation
Abstract: Schizophrenia is a complex disorder, with several genes putatively associated \nwith the pathogenesis of the disorder. A large genome-wide association study \n(O’Donovan et al. 2008) identified ZNF804A as a candidate gene for \nschizophrenia (meta-analysis p = 1.61 x 10-7). The association of the gene with \nschizophrenia (and bipolar disorder) has since been successfully replicated \nseveral times, confirming the association (Riley et al., 2010; Steinberg et al., \n2010; Zhang et al., 2010, Williams et al., 2011). \nThe aim of this thesis is to create and provide preliminary assessments of \na mouse model of the murine form of ZNF804A, Zfp804a. A mutagenised DNA \narchive derived from mice treated with N-ethyl-N-nitrosourea (ENU) held at the \nMRC Mammalian Genetics Unit, Harwell, was screened for mutations in Zfp804a. \nTwo mutations (C59X and C417Y) were selected for re-derivation based upon \nthe estimated impact upon the protein. The mutations were backcrossed onto a \nC57Bl/6J background for three successive generations using a panel of genetic \nmarkers to aid selection for the highest level of C57Bl/6J congenicity (and \ntherefore speed up the backcrossing process). G4 mice were tested in the study. \nPreliminary assessments of the fourth generation intercross cohort \nrevealed, most notably, that the mice breed well, have no gross physical deficits \nand that male Zfp804aC59X/C59X mutants appeared less anxious than other groups \nin the elevated plus maze and performed better than other groups on the \nRotaRod. \nInitial indications show that Zfp804a may indeed influence behaviour and \ncognition however further work is necessary to expand upon these findings with \nlarger samples.
Author: Tamara Al‐Janabi
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1533049927