title: Analysis of gene expression in Ca2+-dependent activator protein for secretion 2 (Cadps2) knockout cerebellum using GeneChip and KEGG pathways.
abstract: In the mouse cerebellum, Ca2+-dependent activator protein for secretion 2 (CADPS2, CAPS2) is involved in regulated secretion from dense-core vesicles (DCVs), which contain neuropeptides including brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). Capds2 knockout (KO) mice show impaired cerebellar development in addition to autistic-like behavioral phenotypes. To understand the molecular impact caused by loss of Capds2, we analyzed gene expression profiles in the Capds2 KO cerebellum using a GeneChip microarray and the KEGG Pathway database. Significant differential expression was observed in 1211 of 22,690 (5.34%) genes represented on the chip. The expression levels of exocytosis-related genes (Stx5a, Syt6), genes encoding secretory (Fgf2, Fgf4, Edn2) and synaptic proteins (Grin2b, Gabbr1), neurotrophin signaling-associated genes (Sos1, Shc1, Traf6, Psen2), and a gene for Rett syndrome (Mecp2) were significantly changed. Taken together, these results suggest that deregulated gene expression caused by loss of Capds2 may cause developmental deficits and/or pathological symptoms, resulting in autistic-like phenotypes.
authors.affiliation: Advanced Scientific Research Leaders Development Unit, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan. Electronic address: sadakata-1024@umin.ac.jp.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Sadakata
authors.affiliation: Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Shinoda
authors.affiliation: Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Ishizaki
authors.affiliation: Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Teiichi
authors.initials: T
authors.lastname: Furuichi
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism*; D030541:Databases, Genetic; D005089:Exocytosis / Q000502:physiology; D015870:Gene Expression / Q000502:physiology*; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C538900:CAPS2 protein, rat; D002135:Calcium-Binding Proteins; D009419:Nerve Tissue Proteins
keywords: Autism; Cadps2; GeneChip; KEGG; Neurotrophin; Secretion