Bcl-x is required for proper development of the mouse: Substantia nigra

Joseph M. Savitt, Susie S. Jang, Weitong Mu, Valina L. Dawson, Ted M. Dawson

Research output: Contribution to journalArticlepeer-review

Abstract

Recent findings have uncovered a role for the Bcl-x gene in the survival of dopaminergic neurons. The exact nature of this role has been difficult to examine because of the embryonic lethality of Bcl-x gene disruption in mouse models. Here we report the generation of catecholaminergic cell-specific conditional Bcl-x gene knock-out mice using Cre-lox recombination technology. First we produced transgenic mice that express Cre recombinase from an exogenous rat tyrosine hydroxylase promoter (TH-Cre mice). These mice were crossed to Z/AP and Z/EG reporter mouse strains to verify catecholaminergic (TH-positive) cell-specific Cre expression. The TH-Cre mice then were mated to mice possessing the Bcl-x gene flanked by loxP sites, thereby producing offspring with Bcl-x deletion limited to catecholaminergic cells. The resulting mice are viable but have one-third fewer catecholaminergic neurons than do control animals. They demonstrate a deficiency in striatal dopamine and also tend to be smaller and have decreased brain mass when compared with controls. Surprisingly, surviving neurons were found that lacked Bcl-x immunoreactivity, thereby demonstrating that this gene is dispensable for the ongoing survival of a subpopulation of catecholaminergic cells.

Original languageEnglish (US)
Pages (from-to)6721-6728
Number of pages8
JournalJournal of Neuroscience
Volume25
Issue number29
DOIs
StatePublished - Jul 20 2005

Keywords

  • Bcl-x
  • Catecholamine
  • Dopamine
  • Parkinson
  • Substantia nigra
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Neuroscience(all)

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