Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk.
To understand the pathophysiology of neuropsychiatric disorders such as schizophrenia requires consideration of multiple genetic and non-genetic factors. However, very little is known about the consequences of combining models of synaptic dysfunction with controlled environmental manipulations. Ther...
| Main Authors: | , |
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| Format: | Journal article |
| Language: | English |
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Oxford University Press
2009
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| _version_ | 1797083551877824512 |
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| author | Oliver, P Davies, K |
| author_facet | Oliver, P Davies, K |
| author_sort | Oliver, P |
| collection | OXFORD |
| description | To understand the pathophysiology of neuropsychiatric disorders such as schizophrenia requires consideration of multiple genetic and non-genetic factors. However, very little is known about the consequences of combining models of synaptic dysfunction with controlled environmental manipulations. Therefore, to generate new insights into gene-environment interactions and complex behaviour, we examined the influence of variable prenatal stress (PNS) on two mouse lines with mutations in synaptosomal-associated protein of 25 kDa (Snap-25): the blind-drunk (Bdr) point mutant and heterozygous Snap-25 knockout mice. Neonatal development was analysed in addition to an assessment of adult behavioural phenotypes relevant to the psychotic, cognitive and negative aspects of schizophrenia. These data show that PNS influenced specific anxiety-related behaviour in all animals. In addition, sensorimotor gating deficits previously noted in Bdr mutants were markedly enhanced by PNS; significantly, these effects could be reversed with the application of anti-psychotic drugs. Moreover, social interaction abnormalities were observed only in Bdr animals from stressed dams but not in wild-type littermates or mutants from non-stressed mothers. These results show for the first time that combining a synaptic mouse point mutant with a controlled prenatal stressor paradigm produces both modified and previously unseen phenotypes, generating new insights into the interactions between genetics and the environment relevant to the study of psychiatric disease. |
| first_indexed | 2024-03-07T01:43:09Z |
| format | Journal article |
| id | oxford-uuid:97865f84-d7fc-423f-9220-b69e766358ee |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:43:09Z |
| publishDate | 2009 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:97865f84-d7fc-423f-9220-b69e766358ee2022-03-27T00:00:20ZInteraction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:97865f84-d7fc-423f-9220-b69e766358eeEnglishSymplectic Elements at OxfordOxford University Press2009Oliver, PDavies, KTo understand the pathophysiology of neuropsychiatric disorders such as schizophrenia requires consideration of multiple genetic and non-genetic factors. However, very little is known about the consequences of combining models of synaptic dysfunction with controlled environmental manipulations. Therefore, to generate new insights into gene-environment interactions and complex behaviour, we examined the influence of variable prenatal stress (PNS) on two mouse lines with mutations in synaptosomal-associated protein of 25 kDa (Snap-25): the blind-drunk (Bdr) point mutant and heterozygous Snap-25 knockout mice. Neonatal development was analysed in addition to an assessment of adult behavioural phenotypes relevant to the psychotic, cognitive and negative aspects of schizophrenia. These data show that PNS influenced specific anxiety-related behaviour in all animals. In addition, sensorimotor gating deficits previously noted in Bdr mutants were markedly enhanced by PNS; significantly, these effects could be reversed with the application of anti-psychotic drugs. Moreover, social interaction abnormalities were observed only in Bdr animals from stressed dams but not in wild-type littermates or mutants from non-stressed mothers. These results show for the first time that combining a synaptic mouse point mutant with a controlled prenatal stressor paradigm produces both modified and previously unseen phenotypes, generating new insights into the interactions between genetics and the environment relevant to the study of psychiatric disease. |
| spellingShingle | Oliver, P Davies, K Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk. |
| title | Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk. |
| title_full | Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk. |
| title_fullStr | Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk. |
| title_full_unstemmed | Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk. |
| title_short | Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk. |
| title_sort | interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the snap 25 mouse mutant blind drunk |
| work_keys_str_mv | AT oliverp interactionbetweenenvironmentalandgeneticfactorsmodulatesschizophrenicendophenotypesinthesnap25mousemutantblinddrunk AT daviesk interactionbetweenenvironmentalandgeneticfactorsmodulatesschizophrenicendophenotypesinthesnap25mousemutantblinddrunk |