| Title: | Bcl-x is required for proper development of the mouse substantia nigra |
| Author(s): | Savitt JM; Jang SS; Mu W; Dawson VL; Dawson TM; |
| Address: | "Institute for Cell Engineering, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA" |
| DOI: | 10.1523/JNEUROSCI.0760-05.2005 |
| ISSN/ISBN: | 1529-2401 (Electronic) 0270-6474 (Print) 0270-6474 (Linking) |
| 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 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" |
| Keywords: | "Animals Cell Count Cell Survival/physiology Dopamine/physiology Gene Deletion *Gene Expression Regulation, Developmental Immunohistochemistry Integrases/genetics Locus Coeruleus/cytology/growth & development/physiology Mice Mice, Inbred Strains Mice, Knoc;" |
| Notes: | "MedlineSavitt, Joseph M Jang, Susie S Mu, Weitong Dawson, Valina L Dawson, Ted M eng NS 38377/NS/NINDS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2005/07/22 J Neurosci. 2005 Jul 20; 25(29):6721-8. doi: 10.1523/JNEUROSCI.0760-05.2005" |
