Mutant DISC1 Inducible Transgenic mouse

Tool Details

*FOR RESEARCH USE ONLY (for other uses, please contact the licensing team)

• Tool name: Mutant DISC1 Inducible Transgenic mouse
• Research fields: Drug development;Neurobiology
• Tool sub type: Mouse
• Disease: Schizophrenia
• Model: Transgenic
• Description: A strong candidate gene for schizophrenia and major mental disorders, disrupted-in-schizophrenia 1 (DISC1) has been implicated in neurodevelopment, including maturation of the cerebral cortex. Translocation mutation may result in loss of DISC1 function via haploinsufficiency or dominant-negative effects of a predicted mutant DISC1 truncated protein product. Transgenic mice with inducible expression of mutant human DISC1 (hDISC1) limited to forebrain regions, including cerebral cortex, hippocampus and striatum were generated using the TET-off gene expression system under the regulation of the CAMKII promoter. Expression of mutant hDISC1 was not shown to be associated with gross neurodevelopmental abnormalities, but did produce mild abnormalities. Compared to their sex-matched littermate controls, mutant hDISC1 transgenic male mice exhibited spontaneous hyperactivity in the open field and alterations in social interaction, and transgenic female mice showed deficient spatial memory. Neuronal and behavioral effects of mutant hDISC1 are consistent with a dominant-negative mechanism, and are similar to some features of schizophrenia.
• Genetic background: B6;SJL-Tg(TRE-CMV-hDISC1) crossed with B6;CBA-Tg(Camk2a-tTA)1Mmay/j mice

Target Details

• Target: DISC1

References

• Pletnikov et al. 2008. Mol Psychiatry. 13(2):173-86, 115. PMID: 17848917.