Mice unable to synthesize norepinephrine (NE) and epinephrine due to targeted disruption of the dopamine beta-hydroxylase gene, Dbh, were used to critically test roles for NE in mediating acute behavioral changes elicited by different classes of antidepressants. To this end, we used the tail suspension test, one of the most widely used paradigms for assessing antidepressant activity and depress...

CRISPR/Cas9 mediated DNA double strand cutting is emerging as a powerful approach to increase rates of homologous recombination of large targeting vectors, but the optimization of parameters, equipment and expertise required remain barriers to successful mouse generation by single-step zygote injection. Here, we sought to apply CRISPR/Cas9 methods to traditional embryonic stem (ES) cell targeti...

In order to characterize the specificity of expression of the neurotransmitter biosynthetic gene dopamine beta-hydroxylase (DBH), the identification of proteins that interact with the DB1 enhancer was initiated. A homeobox-containing cDNA was isolated from a PC12 expression cDNA library screened with the DB1 enhancer. The homeodomain is a member of the paired-like class, and is encoded by sever...

Norepinephrine (NE) is thought to play an important role in the pathophysiology of depression, and in the mechanism of action of antidepressant compounds. Previously, we created mice that are unable to synthesize NE and epinephrine due to targeted disruption of the dopamine-beta-hydroxylase gene (Dbh). To specifically test the role of NE in mediating behavioral changes elicited by antidepressan...

Background and aims Corticostriatal-limbic neurocircuitry, emotional and motivational processing, dopaminergic and noradrenergic systems and genetic factors have all been implicated in pathological gambling (PG). However, allelic variants of genes influencing dopaminergic and noradrenergic neurotransmitters have not been investigated with respect to the neural correlates of emotional and motiva...

We have investigated the specification of noradrenergic neurotransmitter identity in neural crest stem cells (NCSCs). Retroviral expression of both wild-type and dominant-negative forms of the paired homeodomain transcription factor Phox2a indicates a crucial and direct role for this protein (and/or the closely related Phox2b) in the regulation of endogenous tyrosine hydroxylase (TH) and dopami...

The roles of norepinephrine (NE) and epinephrine in behavior were investigated by targeted disruption of the dopamine beta-hydroxylase (Dbh) gene, thereby eliminating these compounds in vivo. Most heterozygous pups born to Dbh-/- females died within several days of birth and were often found scattered within the bedding. Potential causes including deficits in olfaction and lactation were not ap...

DBH is a candidate gene in Parkinson’s disease (PD) and contains a putative functional polymorphism (-1021C3T) that has been reported to modify PD susceptibility. We examined 1021C3T in a sample of 1,244 PD patients and 1,186 unrelated control subjects. There was no significant difference in allele (p 0.14) or genotype (p 0.26) frequencies between the two groups. A similar result was obtained a...

objective: interaction between genetic and environmental factors is considered as major factors in schizophrenia (scz). it has been shown that dopaminergic and noradrenergic neurotransmission dysfunction play an essential role in the scz pathogenesis. this study aimed to find the impact of functional 19-bp insertion/deletion (ins/del) polymorphism in dopamine beta-hydroxylase (dbh) gene on scz ...

The anti-alcoholism medication, disulfiram (Antabuse), decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH), the enzyme that converts dopamine (DA) to norepinephrine (NE) in noradrenergic neurons. The goal of this study was to test the e...