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Publication : Generation and characterization of conditional heparin-binding EGF-like growth factor knockout mice.

First Author  Oyagi A Year  2009
Journal  PLoS One Volume  4
Issue  10 Pages  e7461
PubMed ID  19829704 Mgi Jnum  J:154094
Mgi Id  MGI:4367278 Doi  10.1371/journal.pone.0007461
Citation  Oyagi A, et al. (2009) Generation and characterization of conditional heparin-binding EGF-like growth factor knockout mice. PLoS One 4(10):e7461
abstractText  Recently, neurotrophic factors and cytokines have been shown to be associated in psychiatric disorders, such as schizophrenia, bipolar disorder, and depression. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family, serves as a neurotrophic molecular and plays a significant role in the brain. We generated mice in which HB-EGF activity is disrupted specifically in the ventral forebrain. These knockout mice showed (a) behavioral abnormalities similar to those described in psychiatric disorders, which were ameliorated by typical or atypical antipsychotics, (b) altered dopamine and serotonin levels in the brain, (c) decreases in spine density in neurons of the prefrontal cortex, (d) reductions in the protein levels of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor and post-synaptic protein-95 (PSD-95), (e) decreases in the EGF receptor, and in the calcium/calmodulin-dependent protein kinase II (CaMK II) signal cascade. These results suggest the alterations affecting HB-EGF signaling could comprise a contributing factor in psychiatric disorder.
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