Susceptibility genes for schizophrenia: Characterisation of mutant mouse models at the level of phenotypic behaviour

Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene

“…22 Finally, mouse models with disruptions in NRG1-ERBB4 signaling appear to capture some of the behavioral phenotypes associated with schizophrenia, and in certain cases these altered behaviors can be ameliorated by antipsychotics. 1,[23][24][25] Altogether, the data support a role for abnormal NRG1-ERB signaling in schizophrenia. Dissecting the pathways of NRG1-ERB signaling in the central nervous system may therefore contribute to the elucidation of pathways of schizophrenia susceptibility and may also reveal targets for interventions.…”

Exploratory and habituation phenotype of heterozygous and homozygous COMT knockout mice

“…The functional roles of genes such as NRG1 and COMT can be investigated through the phenotype of mice with targeted gene deletion [knockout; 1,2,22]. Phenotypic studies in COMT knockouts have involved behavioural paradigms which include general motor activity, anxiety, aggression and sensorimotor gating [8,10,14].…”

“…The value of an ethologically based approach to behavioural characterisation of mutant mice is increasingly recognised. It can identify novel phenotypic effects and resolve apparent inconsistencies in phenotype [4,7,22,23]. We have developed and applied such an approach to mice with knockout of each of the five DA receptor subtypes and components mediating DA receptor signal transduction [28].…”

Evidence that many of the DISC1 isoforms in C57BL/6J mice are also expressed in 129S6/SvEv mice

“…3 The minor behavioral abnormality resulting from the 25-bp deletion is in contrast to the results of three independent groups who have generated partial lossof-function models by expressing dominant-negative DISC1 constructs and obtained substantial changes in behavior, including deficits in prepulse inhibition, latent inhibition and working memory. 4 Moreover, the absence of obvious anatomical changes in the mutant mice 1 conflicts with cellular models based on the knockdown of DISC1 or expression of dominantnegative DISC1, which disrupts developmental processes critical for normal cortical architecture. 5 Thus, if the 25-bp deletion completely abolishes the fulllength DISC1 protein that is crucial for proper neurodevelopment, why are there such small phenotypic changes in mice with this mutation?…”

“…One proposed susceptibility locus occurs on chromosome 4q35. [2][3][4] Blair et al 1 undertook positional cloning, association tests and gene expression assays and found support for a role of the FAT gene, that resides within that chromosomal region, in relation to BPAD.…”