Generation and Characterization of Conditional Heparin-Binding EGF-Like Growth Factor Knockout Mice 英文参考文献.docVIP
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Generation and Characterization of Conditional Heparin-Binding EGF-Like Growth Factor Knockout Mice 英文参考文献
GenerationandCharacterizationofConditionalHeparin-
BindingEGF-LikeGrowthFactorKnockoutMice
AtsushiOyagi1,YasuhisaOida1,KenichiKakefuda1,MasamitsuShimazawa1,NorifumiShioda2 ,Shigeki
Moriguchi2,KiyoyukiKitaichi3,DaisukeNanba4,KazumasaYamaguchi5,YasuhideFuruta6 ,Kohji
Fukunaga2,ShigekiHigashiyama4,HideakiHara1*
1Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan, 2Department of Pharmacology, Graduate School of
Pharmaceutical Sciences, Tohoku University, Sendai, Japan, 3Department of Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki International University,
Nagasaki,Japan,4DepartmentofBiochemistryandMolecularGenetics,EhimeUniversityGraduateSchoolofMedicine,Ehime,Japan,5NihonBioresearchCenterInc.,
Gifu,Japan,6DepartmentofBiochemistryandMolecularBiology,TheUniversityofTexasM.D.AndersonCancerCenter,Houston,Texas,UnitedStatesofAmerica
Abstract
Recently, neurotrophic factors and cytokines have been shown to be associated in psychiatric disorders, such as
schizophrenia,bipolardisorder,anddepression.Heparin-bindingepidermalgrowthfactor-likegrowthfactor(HB-EGF)isa
memberoftheEGFfamily,servesasaneurotrophicmolecularandplaysasignificantroleinthebrain.Wegeneratedmicein
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
prefrontalcortex,(d)reductionsintheproteinlevelsoftheNR1subunitoftheN-methyl-D-aspartate(NMDA)receptorand
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
contributingfactorinpsychiatricdisorder.
Citation:OyagiA,OidaY,Ka
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