Transgenic mice engineered to target Cre/loxP‐mediated DNA recombination into catecholaminergic neurons

Gelman, Diego M.; Noaín, Daniela; Avale, María Elena; Otero, Verónica; Low, Malcolm J.; Rubinstein, Marcelo

doi:10.1002/gene.10217

Cited by 50 publications

(51 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This along with the generation of multiple mouse lines showing similar Cre localization proves that the TH promoter is driving Cre expression. Also, mice described previously and produced in a similar manner demonstrate Cre localization that parallels that seen here (Gelman et al, 2003).…”

Section: Discussionsupporting

confidence: 84%

“…Several other areas that are not typically thought to have active TH expression, including the lateral septal nucleus, accessory olfactory bulb, suparafascicular thalamus, and pretectal area, also stain for Cre activity, possibly as a result of TH promoter activity in precursor cell populations or ectopic expression from the exogenous TH promoter. Indeed, ectopic expression driven by the exogenous TH promoter has been described previously (Min et al, 1994;Gelman et al, 2003). Interestingly, some cells closely clustered around and within TH-positive nuclei (locus ceruleus and substantia nigra) demonstrate Cre activity, although they do not stain for TH protein (Fig.…”

Section: Tissue-specific Expression Of Cre Recombinase In Catecholamimentioning

confidence: 54%

See 1 more Smart Citation

Bcl-xIs Required for Proper Development of the Mouse Substantia Nigra

et al. 2005

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 84%

Section: Tissue-specific Expression Of Cre Recombinase In Catecholamimentioning

confidence: 54%

Bcl-xIs Required for Proper Development of the Mouse Substantia Nigra

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Lmx1b gene deletion mutant (Chen et al, 1998), Lmx1b flox/flox (Guo et al, 2007), Nestin-Cre (Isaka et al, 1999), TH-Cre (Gelman et al, 2003), and Dat cre/ϩ (Zhuang et al, 2005) Nestin CKO) mice were obtained. The age of embryos was determined according to the plug date (considered to be E0.5).…”

Section: Methodsmentioning

confidence: 99%

Retracted:Lmx1b-Controlled Isthmic Organizer Is Essential for Development of Midbrain Dopaminergic Neurons

Guo¹,

Qiu²,

Shi

et al. 2008

J. Neurosci.

View full text Add to dashboard Cite

The LIM homeodomain transcription factor Lmx1b has been suggested to be required for the differentiation of midbrain dopaminergic (mDA) neurons. However, whether the loss of mDA neurons in Lmx1b Ϫ/Ϫ mice is due to its intrinsic role in the mDA lineage or to a consequence of the malformations caused by the earlier mid/hindbrain patterning defects remains to be clarified. We report here that Lmx1b expression in mDA neurons is dispensable for their differentiation and maintenance, and the loss of mDA neurons in Lmx1b

show abstract

“…24 Briefly, mice were transcardiacally perfused with 4% paraformaldehyde. Brains were removed, postfixed and cryoprotected.…”

Section: Neurochemical Assaysmentioning

confidence: 99%

The dopamine D4 receptor is essential for hyperactivity and impaired behavioral inhibition in a mouse model of attention deficit/hyperactivity disorder

et al. 2003

View full text Add to dashboard Cite

The dopamine D4 receptor (D4R) is a candidate gene for attention deficit/hyperactivity disorder (ADHD) based on genetic studies reporting that particular polymorphisms are present at a higher frequency in affected children. However, the direct participation of the D4R in the onset or progression of ADHD has not been tested. Here, we generated a mouse model with high face value to screen candidate genes for the clinical disorder by neonatal disruption of central dopaminergic pathways with 6-hydroxydopamine (6-OHDA). The lesioned mice exhibited hyperactivity that waned after puberty, paradoxical hypolocomotor responses to amphetamine and methylphenidate, poor behavioral inhibition in approach/avoidance conflict tests and deficits in continuously performed motor coordination tasks. To determine whether the D4R plays a role in these behavioral phenotypes, we performed 6-OHDA lesions in neonatal mice lacking D4Rs (Drd4 À/À ). Although striatal dopamine contents and tyrosine hydroxylasepositive midbrain neurons were reduced to the same extent in both genotypes, Drd4 À/À mice lesioned with 6-OHDA did not develop hyperactivity. Similarly, the D4R antagonist PNU-101387G prevented hyperactivity in wild-type 6-OHDA-lesioned mice. Furthermore, wild-type mice lesioned with 6-OHDA showed an absence of behavioral inhibition when tested in the open field or the elevated plus maze, while their Drd4 À/À siblings exhibited normal avoidance for the unprotected areas of these mazes. Together, our results from a combination of genetic and pharmacological approaches demonstrate that D4R signaling is essential for the expression of juvenile hyperactivity and impaired behavioral inhibition, relevant features present in this ADHD-like mouse model.

show abstract

Transgenic mice engineered to target Cre/loxP‐mediated DNA recombination into catecholaminergic neurons

Cited by 50 publications

References 14 publications

Bcl-xIs Required for Proper Development of the Mouse Substantia Nigra

Bcl-xIs Required for Proper Development of the Mouse Substantia Nigra

Retracted:Lmx1b-Controlled Isthmic Organizer Is Essential for Development of Midbrain Dopaminergic Neurons

The dopamine D4 receptor is essential for hyperactivity and impaired behavioral inhibition in a mouse model of attention deficit/hyperactivity disorder

Contact Info

Product

Resources

About