Detection of FGF reception 2 splice variants in human post-mortem brain regions and evaluation of differential variant expression in depressed subjects relative to controls
SJ Evans; J Li; PV Choudary; MP Vawter; H Tomita; RC Thompson; JF Lopez; RC Meyers; EG Jones; WE Bunney; H Akil and SJ Watson.
Society for Neuroscience annual meeting. 2005.
There is increasing evidence for the roles of growth factors in psychiatric illness and the mechanism of action of mood stabilizing drugs. We have previously reported the dysregulation of several transcripts in the fibroblast growth factor (FGF) system in post-mortem brains of depressed subjects relative to controls. FGF receptor 2 (FGFR2) was among the most significant of our previous findings and we have consistently found this transcript to be decreased in several brain areas of depressed subjects. The human FGFR2 gene contains 19 exons and produces as many as 13 splice variants. These variants fall into three main functional classes: first, variants that lack the transmembrane and tyrosine kinase domain and are thought to be soluble receptors; second, variants that contain the Ig IIIc type domain encoded by exon 9; and third variants that contain the Ig IIIb type domain encoded by exon 8. The Ig III type domain confers ligand specificity and thus these latter two variants have different pharmacological profiles based on their use of the IIIc or IIIb domain. In this report we will present PCR based studies to identify which exons are expressed and which splice variants are present in total RNA derived from human cortex (dorsolateral prefrontal and anterior cingulated) and hippocampus. We will also present data on any differential expression of specific exons between depressed and control subjects. The authors are members of the Pritzker Neuropsychiatric Disorders Research Consortium, which is supported by the Pritzker Neuropsychiatric Disorders Research Fund L.L.C. A shared intellectual property agreement exists between this philanthropic fund and the University of Michigan, Stanford University, the Universities of California at Davis and at Irvine, to encourage the development of appropriate findings for research and clinical applications This work is supported by the Pritzker Neuropsychiatric Disorders Research Consortium, NIH Conte center grant #L99MH60398 and a gran t from the National Alliance for Research on Schizophrenia and Depression (NARSAD).