Bcl-x is required for proper development of the mouse substantia nigra.
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.
Savitt
Joseph M
JM
Institute for Cell Engineering, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Jang
Susie S
SS
Mu
Weitong
W
Dawson
Valina L
VL
Dawson
Ted M
TM
D000818:Animals; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D019426:Integrases / Q000235:genetics; D008125:Locus Coeruleus / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D013378:Substantia Nigra / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics* / Q000378:metabolism*
C494812:Bcl2l1 protein, mouse; D051020:bcl-X Protein; D014446:Tyrosine 3-Monooxygenase; C045073:Cre recombinase; D019426:Integrases; D004298:Dopamine