Selective vulnerability of late-generated dopaminergic neurons of the substantia nigra in weaver mutant mice

Shirley A. Bayer, Katherine V. Wills, Lazaros C. Triarhou, Tatyana Verina, James D. Thomas, Bernardino Ghetti

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

In homozygous weaver (wv/wv) mutant mice, nearly 50% of the dopaminergic substantia nigra neurons degenerate by postnatal day 20. We have now determined that the total number of dopaminergic neurons in the ventral midbrains of a litter of obligatory homozygous weaver pups and a litter of normal wild-type control pups indicates that no significant differences are present between groups at birth. To test the hypothesis that the subsequent degeneration of these neurons is linked to their time of origin, [3H]thymidine autoradiography was combined with tyrosine hydroxylase immunocytochemistry to construct neurogenetic timetables on postnatal day 20 in wild-type mice and weaver homozygotes. Both groups have the same span of neurogenesis but have statistically different proportions of neurons generated on specific days. In wild-type mice, more than half of the dopaminergic neurons originate on or after embryonic day 12. In contrast, over two-thirds of the surviving dopaminergic neurons in homozygous weaver mice originate on or before embryonic day 11. Our data suggest that the weaver gene does not interfere with the generation of dopaminergic neurons, but it preferentially kills late-generated dopaminergic neurons between birth and postnatal day 20.

Original languageEnglish (US)
Pages (from-to)9137-9140
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number20
DOIs
StatePublished - Sep 26 1995

    Fingerprint

Keywords

  • [H]thymidine autoradiography
  • animal models
  • neurogenesis
  • neurological mutants
  • tyrosine hydroxylase immunocytochemistry

ASJC Scopus subject areas

  • Genetics
  • General

Cite this