Intranuclear inclusions in subtypes of striatal neurons in Huntington's disease transgenic mice

R6/2 transgenic mice express exon 1 of an abnormal human Huntington's disea se (HD) gene and develop a neurological phenotype similar to HD. These mice develop ubiquitinated neuronal intranuclear inclusions (NII) which might p lay a central role in the pathophysiology of HD. We studied the distributio n of NII in subpopulations of striatal neurons in 12-week-old R6/2 transgen ic mice using fluorescent double label immunohistochemistry. We observed th at most of the Calbindin-D28K positive projection neurons (89%) and the Par valbumin positive interneurons (86%) showed ubiquitinated NII. In interneur ons, however, which contain either choline acetyltransferase, neuronal nitr ic oxide synthase, or Calretinin, the frequency of NII was much lower (22%, 8%, 9%, respectively). Our data suggest that subpopulations of striatal ne urons differ remarkably in their capability of forming ubiquitinated NII. I nterneurons which are known to resist neurodegeneration in HD show less NII . (C) 1999 Lippincott Williams & Wilkins.