Purkinje cell degeneration associated with erythroid ankyrin deficiency in nb/nb mice.

Journal Article

Mice homozygous for the nb mutation (Chromosome 8) have a severe hemolytic anemia and develop a psychomotor disorder at 6 mo of age. The nb/nb mice are deficient in erythroid ankyrin (Ank-1) but, until the present study, the role of Ank-1 and of Ank-2 (brain ankyrin) in disease genesis was unknown. In normal erythroid tissues, we show that two major transcripts are expressed from Ank-1, and one of these is also present at high levels in the cerebellum. By in situ hybridization and immunocytochemistry, Ank-1 localizes to the cerebellar Purkinje cells and, to a lesser extent, the granule cells. In nb/nb mice, Ank-1 transcripts are markedly reduced in both erythroid and neural tissue, and nb/nb Purkinje cells and granule cells are nearly devoid of Ank-1. The neurological syndrome appears concurrently with a dramatic loss of Purkinje cells. Ank-2 maps to Chromosome 3 and its expression is unaffected by the nb mutation. We conclude that Ank-1 is specifically required for Purkinje cell stability and, in its absence, Purkinje cell loss and neurological symptoms appear.

Full Text

Duke Authors

Cited Authors

  • Peters, LL; Birkenmeier, CS; Bronson, RT; White, RA; Lux, SE; Otto, E; Bennett, V; Higgins, A; Barker, JE

Published Date

  • September 1, 1991

Published In

Volume / Issue

  • 114 / 6

Start / End Page

  • 1233 - 1241

PubMed ID

  • 1716634

International Standard Serial Number (ISSN)

  • 0021-9525

Language

  • eng

Conference Location

  • United States