title: Intranuclear inclusions in subtypes of striatal neurons in Huntington's disease transgenic mice.
abstract: R6/2 transgenic mice express exon 1 of an abnormal human Huntington's disease (HD) gene and develop a neurological phenotype similar to HD. These mice develop ubiquitinated neuronal intranuclear inclusions (NII) which might play a central role in the pathophysiology of HD. We studied the distribution of NII in subpopulations of striatal neurons in 12-week-old R6/2 transgenic mice using fluorescent double label immunohistochemistry. We observed that most of the Calbindin-D28K positive projection neurons (89%) and the Parvalbumin positive interneurons (86%) showed ubiquitinated NII. In interneurons, however, which contain either choline acetyltransferase, neuronal nitric oxide synthase, or Calretinin, the frequency of NII was much lower (22%, 8%, 9%, respectively). Our data suggest that subpopulations of striatal neurons differ remarkably in their capability of forming ubiquitinated NII. Interneurons which are known to resist neurodegeneration in HD show less NII.
authors.affiliation: Department of Neurology, University Hospital RWTH Aachen, Germany.
authors.forename: C M
authors.initials: CM
authors.lastname: Kosinski
authors.forename: J H
authors.initials: JH
authors.lastname: Cha
authors.forename: A B
authors.initials: AB
authors.lastname: Young
authors.forename: L
authors.initials: L
authors.lastname: Mangiarini
authors.forename: G
authors.initials: G
authors.lastname: Bates
authors.forename: J
authors.initials: J
authors.lastname: Schiefer
authors.forename: M
authors.initials: M
authors.lastname: Schwarz
mesh_terms: D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology*; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology*; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism / Q000648:ultrastructure*; D007395:Interneurons / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D010320:Parvalbumins / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism
chemical_list: C576498:CALB1 protein, human; C576499:Calb1 protein, mouse; D064092:Calbindin 1; D064026:Calbindins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D014452:Ubiquitins; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D002795:Choline O-Acetyltransferase