Seizure-Related Gene 6 (Sez-6) in Amacrine Cells of the Rodent Retina and the Consequence of Gene Deletion 英文参考文献.docVIP

Seizure-RelatedGene6(Sez-6)inAmacrineCellsofthe RodentRetinaandtheConsequenceofGeneDeletion JennyM.Gunnersen1*,AnnabelKuek1,JoannaA.Phipps2,VickiE.Hammond1,TheresaPuthussery2, EricaL.Fletcher2,Seong-SengTan1 1BrainDevelopment,HowardFloreyInstitute,UniversityofMelbourne,Parkville,Victoria,Australia,2DepartmentofAnatomyCellBiology,UniversityofMelbourne, Parkville,Victoria,Australia Abstract Background:Seizure-relatedgene6(Sez-6)isexpressedinneuronsofthemousebrain,retinaandspinalcord.Inthecortex, Sez-6playsaroleinspecifyingdendriticbranchingpatternsandexcitatorysynapsenumbersduringdevelopment. Methodology/PrincipalFindings:ThedistributionpatternofSez-6intheretinawasstudiedusingapolyclonalantibody that detects the multiple isoforms of Sez-6. Prominent immunostaining was detected in GABAergic, but not in AII glycinergic,amacrinecellsubpopulationsoftheratandmouseretina.Amacrinecellsomatadisplayedadistinctstaining patternwiththeSez-6antibody:adiscrete,oftenroughlytriangular-shapedbrightspotpositionedbetweenthenucleus andtheapicaldendritesuperimposedoverweakergeneralcytoplasmicstaining.Displacedamacrinesintheganglioncell layerwerealsopositiveforSez-6andweakerstainingwasoccasionallyobservedinneuronswiththemorphologyofalpha ganglion cells. Two distinct Sez-6 positive strata were present in the inner plexiform layer in addition to generalized punctatestaining.Certaininnernuclearlayercells,includingbipolarcells,stainedmoreweaklyanddiffuselythanamacrine cells,althoughsomebipolarcellsexhibitedaperinuclear‘‘brightspot’’similartoamacrinecells.Inordertoassesstheroleof Sez-6intheretina,weanalyzedthemorphologyoftheSez-6knockoutmouseretinawithimmunohistochemicalmarkers andcomparedganglioncelldendriticarborpatterninginSez-6nullretinaewithcontrols.ThefunctionalimportanceofSez- 6wasassessedbydark-adaptedpaired-flashelectroretinography(ERG). Conclusions: In summary, we have reported the detailed expression pattern of a novel retinal marker with broad cell specificity, useful for retinal