Brain, Vol. 125, No. 7, 1534-1543,
July 2002
© 2002 Guarantors of Brain
Two populations of neuronal intranuclear inclusions in SCA7 differ in size and promyelocytic leukaemia protein content
1 Laboratoire de Neuropathologie Raymond Escourolle, 2 INSERM U289, 3 U106, 4 U360, Association Claude Bernard, 5 Fédération de Neurologie and 6 Département de Génétique, Cytogénétique et Embryologie, Hôpital de la Salpêtrière, 7 CNRS UPR 9051 Centre Hayem Hôpital St Louis, Paris, 8 Institut de Génétique et de Biologie Moléculaire (IGBMC), CNRS, INSERM, Université Louis Pasteur, Illkirch, CU de Strasbourg, France, 9 Division of Neuropathology, The Jikei University School of Medicine, Tokyo, Japan and 10 Neurogenetics Unit, Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden
Correspondence to: A. Brice, INSERM U 289, Hôpital de la Salpêtrière, 47, boulevard de l’Hôpital, 75651 Paris, Cedex 13, France E-mail: brice{at}ccr.jussieu.fr
Spinocerebellar ataxia type 7 (SCA7) is a hereditary progressive cerebellar ataxia with retinal degeneration associated with an abnormally expanded polyglutamine stretch. Neuronal intranuclear inclusions (NIIs), as in other polyglutamine diseases, are pathological hallmarks of these disorders. NIIs in polyglutamine diseases contain not only the protein with the expanded polyglutamine stretch but also other types of proteins. Several chaperone proteins related to the ubiquitin proteasome pathway, transcription factors and nuclear matrix proteins have been detected in NIIs. The composition of NIIs might reflect the process of NII formation and part of the pathogenesis of these diseases. To investigate how these proteins relate to the pathogenesis of SCA7, we performed immunohistochemical analyses of the composition of NIIs in two cases of SCA7. We demonstrated that there are two types of NIIs in SCA7 that differ in size and immunoreactivity to promyelocytic leukaemia protein (PML), one of the essential components of nuclear bodies (NBs; also called PML oncogenic domains). Small and large NIIs contained ataxin-7, human DnaJ homologue 2 (HDJ-2) and proteasome subunit 19S. In contrast, PML was found only in small NIIs. CREB-binding protein (CBP), another component of NBs, was distributed like PML in NIIs. Our results suggest that NIIs are formed by the accumulation of ataxin-7 in NBs, which become enlarged as they recruit related proteins.
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