TY - JOUR T1 - <em>Bcl-x</em> Is Required for Proper Development of the Mouse Substantia Nigra JF - The Journal of Neuroscience JO - J. Neurosci. SP - 6721 LP - 6728 DO - 10.1523/JNEUROSCI.0760-05.2005 VL - 25 IS - 29 AU - Joseph M. Savitt AU - Susie S. Jang AU - Weitong Mu AU - Valina L. Dawson AU - Ted M. Dawson Y1 - 2005/07/20 UR - http://www.jneurosci.org/content/25/29/6721.abstract N2 - 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 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. ER -