Homozygous Mutant DISCI Mice
JHU REF: C11617
Invention Novelty:
The disclosed technologies are two tangible materials that are improved homozygous mouse strains with inducible expression of mutant human Disrupted-In-Schizophrenia-1 (hDISC1) using Tet-off system under the control of CAMKII.
Value Proposition:
The disclosed materials are improved mouse strains of inducible expression of hDISC1 to facilitate the research in pathogenesis and preclinical therapeutic experiments of schizophrenia.
Technical Details:
Johns Hopkins researchers have generated homozygous mouse strains carrying mutant hDISC1 without gross developmental defects. In these strains, the expression of mutant hDISC1 is restricted to forebrain regions using TET-off system under the control of CAMKII. In addition, the expression can be suppressed by feeding the mice with doxycycline (DOX).
Linkage and association of DISC1 or the region of the DISC1 locus to schizophrenia and psychiatric illnesses have been implicated in a number of genetic analyses and family pedigrees. DISC1 protein is expressed mainly in forebrain regions and is thought to act as a scaffold protein to mediate protein-protein binding. Many in vitro and in vivo studies have indicated that DISC1 affects neurotransmission, localization, and density of dopamine (DA) neurons via AKT/GSK-3β signaling.
These transgenic animals allow selective control of mutant hDISC1 expression in forebrain neurons and, herein provides a valuable research tool to study pathogenesis of schizophrenia and to conduct experimental therapeutics for the disease.
Looking for Partners: To license these materials for research purposes.
Stage of Development: Tangible material
Data Availability: Animal data
Patent Status: None- tangible material
Publication(s)/Associated Cases:
1. “Mutant DISC1 affects methamphetamine-induced sensitization and conditioned place preference: a comorbidity model.” Pogorelov VM, Nomura J, Kim J, Kannan G, Ayhan Y, Yang C, Taniguchi Y, Abazyan B, Valentine H, Krasnova IN, Kamiya A, Cadet JL, Wong DF, Pletnikov MV. Neuropharmacology. 2011 Feb 17.
2. “Prenatal interaction of mutant DISC1 and immune activation produces adult psychopathology.” Abazyan B, Nomura J, Kannan G, Ishizuka K, Tamashiro KL, Nucifora F, Pogorelov V, Ladenheim B, Yang C, Krasnova IN, Cadet JL, Pardo C, Mori S, Kamiya A, Vogel MW, Sawa A, Ross CA, Pletnikov MV. Biol Psychiatry. 2010 Dec 15;68(12):1172-81.
