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Animal Models

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Animal Model: DISC1 L100P Missense Mutation
Preparation Type: Genetic Preparations
DA-related behavior: Increased locomotor activity; enhanced response to amphetamine
Gating: Disrupted PPI; Decreased startle amplitude
Cognitive behavior: Working memory impaired in T-maze; normal spatial learning in water maze
Molecular/morphological signature: Reduced brain volume; reduced dendritic spine density; increased striatal dopamine receptors
Response to APD: Clozapine and haloperidol reversed PPI deficit; genetic inactivation of GSK-3alpha improves PPI, hyperactivity and dendritic spine abnormalities
Citations: Lee FH, Zai CC, Cordes SP, Roder JC, Wong AH. Abnormal interneuron development in disrupted-in-schizophrenia-1 L100P mutant mice. Mol Brain. 2013 Apr 30;6:20. doi: 10.1186/1756-6606-6-20. Abstract

Lee FH, Kaidanovich-Beilin O, Roder JC, Woodgett JR, Wong AH. Genetic inactivation of GSK3α rescues spine deficits in Disc1-L100P mutant mice. Schizophr Res. 2011 Jun;129(1):74-9. Abstract

Lee FH, Fadel MP, Preston-Maher K, Cordes SP, Clapcote SJ, Price DJ, Roder JC, Wong AH. Disc1 point mutations in mice affect development of the cerebral cortex. J Neurosci. 2011 Mar 2;31(9):3197-206. doi: 10.1523/JNEUROSCI.4219-10.2011. Abstract

Lipina TV, Haque FN, McGirr A, Boutros PC, Berger T, Mak TW, Roder JC, Wong AH. Prophylactic valproic acid treatment prevents schizophrenia-related behaviour in Disc1-L100P mutant mice. PLoS One. 2012;7(12):e51562. Abstract

Haque FN, Lipina TV, Roder JC, Wong AH. Social defeat interacts with Disc1 mutations in the mouse to affect behavior. Behav Brain Res. 2012 Aug 1;233(2):337-44. Abstract

Walsh J, Desbonnet L, Clarke N, Waddington JL, O'Tuathaigh CM. Disruption of exploratory and habituation behavior in mice with mutation of DISC1: an ethologically based analysis. J Neurosci Res. 2012 Jul;90(7):1445-53. Abstract

Clapcote SJ, Lipina TV, Millar JK, Mackie S, Christie S, Ogawa F, Lerch JP, Trimble K, Uchiyama M, Sakuraba Y, Kaneda H, Shiroishi T, Houslay MD, Henkelman RM, Sled JG, Gondo Y, Porteous DJ, Roder JC. Behavioral phenotypes of Disc1 missense mutations in mice. Neuron. 2007 May 3;54(3):387-402. Abstract


December 20, 2014
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