Susceptibility genes for schizophrenia: characterisation of mutant mouse models at the level of phenotypic behaviour.
A wealth of evidence indicates that schizophrenia is heritable. However, the genetic mechanisms involved are poorly understood. Furthermore, it may be that genes conferring susceptibility interact with one another and with non-genetic factors to modulate risk status and/or the expression of symptoms. Genome-wide scanning and the mapping of several regions linked with risk for schizophrenia have led to the identification of several putative susceptibility genes including neuregulin-1 (NRG1), dysbindin (DTNBP1), regulator of G-protein signalling 4 (RGS4), catechol-o-methyltransferase (COMT), proline dehydrogenase (PRODH) and disrupted-in-schizophrenia 1 (DISC1). Genetic animal models involving targeted mutation via gene knockout or transgenesis have the potential to inform on the role of a given susceptibility gene on the development and behaviour of the whole organism and on whether disruption of gene function is associated with schizophrenia-related structural and functional deficits. This review focuses on data regarding the behavioural phenotype of mice mutant for schizophrenia susceptibility genes identified by positional candidate analysis and the study of chromosomal abnormalities. We also consider methodological issues that are likely to influence phenotypic effects, as well as the limitations associated with existing molecular techniques.
O'Tuathaigh
Colm M P
CM
Molecular & Cellular Therapeutics and Research Institute, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland.
Babovic
Daniela
D
O'Meara
Gillian
G
Clifford
Jeremiah J
JJ
Croke
David T
DT
Waddington
John L
JL
D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005824:Genetics, Behavioral / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020412:Multifactorial Inheritance / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D010641:Phenotype; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology
D009419:Nerve Tissue Proteins