| First Author | Tueting P | Year | 2006 |
| Journal | Neurosci Biobehav Rev | Volume | 30 |
| Issue | 8 | Pages | 1065-77 |
| PubMed ID | 16769115 | Mgi Jnum | J:241771 |
| Mgi Id | MGI:5903598 | Doi | 10.1016/j.neubiorev.2006.04.001 |
| Citation | Tueting P, et al. (2006) Reelin down-regulation in mice and psychosis endophenotypes. Neurosci Biobehav Rev 30(8):1065-77 |
| abstractText | Reelin, a large glycoprotein secreted by telencephalic GABAergic neurons, plays an important role in neuronal guidance embryonically and in synaptic plasticity postnatally. The reeler heterozygous mouse (+/rl) appears superficially normal but has been of interest as an animal model for psychosis since the discovery that reelin is 50% down-regulated in postmortem psychotic brain. Brain abnormalities in +/rl are similar to psychotic brain and include a reduction in glutamic acid de carboxylase 67 (GAD67), dendritic arbors and spine density in cortex and hippocampus, and abnormalities in synaptic function including long-term potentiation (LTP). In spite of these abnormalities, behavioral abnormalities in +/rl are subtle and controversial. Recent findings indicate that the reelin (RELN) and GAD67 promoters are hypermethylated in GABAergic neurons of psychotic postmortem brain and that DNA methyltransferase 1 (DNMT1) is up-regulated. Hypermethlyation of RELN and GAD67 promoters can be induced by treating mice with methionine, and these mice display brain and behavioral abnormalities similar to +/rl. Thus, an animal model that combines genetic heterozygocity with epigenesis holds promise for understanding the role of Reelin down-regulation in psychosis. |
