Disease relevance of Dbh

• The dopamine beta-hydroxylase gene promoter directs expression of E. coli lacZ to sympathetic and other neurons in adult transgenic mice [1].
• TH and DBH immunoreactivities were found in almost all chief cells and a few ganglion cells, and in relatively numerous varicose nerve fibers of the carotid body [2].
• Concomitant elevation of tyrosine hydroxylase and dopamine beta-hydroxylase by cyclic AMP in cultured mouse neuroblastoma cells [3].
• Mice lacking dopamine beta-hydroxylase (Dbh-/-), the enzyme responsible for synthesizing norepinephrine and epinephrine from dopamine, were treated with leptin (20 microg/g body weight/day) for 3 days before they were euthanized [4].
• In DBH-/- and alpha1B-AR-/- mice, increases in lumen area, circumference, and hypertrophy of the media and adventitia were reduced by 50-91%, resulting in restoration of wall tension to nearly normal (DBH-/-) or normal (alpha1B-AR-/-) [5].

Psychiatry related information on Dbh

• A deficit in maternal behavior was confirmed by the lack of pup retrieval exhibited by Dbh-/- virgin females [6].
• Amphetamine (2 mg/kg) elicited greater locomotor activity in Dbh-/- mice compared to controls, whereas 5 mg/kg caused stereotypy in Dbh-/- mice, which is only observed in control mice at higher doses [7].
• In contrast, Dbh -/- mice displayed a specific deficit in a social discrimination task and had a nearly complete absence of resident-intruder aggression [8].
• We tested dopamine beta-hydroxylase knockout (Dbh -/-) mice that lack NA in various social behavior paradigms [8].
• To determine whether noradrenaline (NA) is an essential neurotransmitter for addictive and appetitive behaviors, we measured drug and food seeking in transgenic mice lacking dopamine beta-hydroxylase (Dbh), the enzyme responsible for synthesizing NA [9].

High impact information on Dbh

• 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 [6].
• As a potential model for obesity, we generated mice that cannot synthesize noradrenaline or adrenaline by inactivating the gene that encodes dopamine beta-hydroxylase [10].
• Mortality was due to lack of noradrenaline in utero because it could be prevented by treatment with dihydroxyphenylserine, a precursor that can be converted to noradrenaline in the absence of dopamine beta-hydroxylase [11].
• Biochemically, the selective induction of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase key enzymes in catecholamine biosynthesis is one of its most characteristic effects [12].
• To examine the role of the ET(B) receptor in the response to acidosis in vivo, the present studies examined ET(B) receptor-deficient mice, rescued from neonatal lethality by expression of a dopamine beta-hydroxylase promoter/ET(B) receptor transgene (Tg/Tg:ET(B)(-/-) mice) [13].

Chemical compound and disease context of Dbh

• We suggest that the primary difference in Dbh-/- mice is chronic hyperinsulinemia associated with an altered glucose set point [14].
• Antagonists of DA, but not 5-HT, receptors attenuated the locomotor hypersensitivity to cocaine in Dbh-/- mice [15].
• As a behavioral consequence of these neurochemical changes, Dbh-/- mice were hypersensitive to the psychomotor, rewarding, and aversive effects of cocaine, as measured by locomotor activity and conditioned place preference [15].
• When exposed to the convulsant flurothyl, Dbh +/- mice fed the KD had significantly longer latencies to myoclonic jerk (MJ) and generalized clonic-tonic (CT) seizures than Dbh +/- mice fed normal chow [16].
• The hyperkinesia following treatment with reserpine and a higher dose of L-Dopa (250 mg/kg i.p.) was probably due to stimulation of both dopamine and noradrenaline receptors since the dopamine-beta-hydroxylase inhibitor FLA-63 partly reduced the effect of L-Dopa [17].

Biological context of Dbh

• The loci for gelsolin and dopamine beta-hydroxylase therefore form part of the conserved synteny between HSA9q and MMU2 [18].
• Comparative mapping of mouse chromosome 2 and human chromosome 9q: the genes for gelsolin and dopamine beta-hydroxylase map to mouse chromosome 2 [18].
• The N-terminal segment of Arix is essential for transcriptional regulatory activity, and this region bears 50% identity with NBPhox, suggesting a similar mechanism of transcriptional activation of the DBH gene [19].
• In separate experiments, leptin produced comparable reductions in food intake in both Dbh+/- and Dbh-/- mice, illustrating that norepinephrine is not required for leptin's effect on food intake [4].
• The density of beta-AR was up-regulated to varying degrees in many brain regions of Dbh-/- mice compared to the heterozygotes [20].

Anatomical context of Dbh

• The cholinergic agonist pilocarpine and electrostimulation of the sciatic nerve both elicited a sweat response in adult DBH -/- mice that was indistinguishable from the response of controls, and the cholinergic antagonist atropine effectively blocked these responses [21].
• In MObr/y, a superficial plexus of DBH immunoreactive fibers was more pronounced than in controls but there were no DBH immunoreactive neurons in the cerebral cortex or striatum in any of the mice examined [22].
• Effects of systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to mice on tyrosine hydroxylase, L-3,4-dihydroxyphenylalanine decarboxylase, dopamine beta-hydroxylase, and monoamine oxidase activities in the striatum and hypothalamus [23].
• Since no overlapping DBH-positive fibers were found here, these TH-positive nerve endings may be dopaminergic [24].
• Immunostaining mouse cochleas for tyrosine hydroxylase (TH) and dopamine beta-hydroxylase suggests that there is a rich adrenergic innervation throughout the auditory nerve trunk and a small dopaminergic innervation of the sensory cell areas [25].

Associations of Dbh with chemical compounds

• Dopamine beta-hydroxylase (DBH) catalyzes the final step in the biosynthesis of norepinephrine, the principal classic neurotransmitter of peripheral sympathetic neurons [1].
• We used mice lacking the gene coding for dopamine beta-hydroxylase, the enzyme responsible for synthesis of NA from dopamine, to reexamine the consequences of a lack of NA on pain behavior [26].
• Some had dopamine beta-hydroxylase-like (DBH-IR) immunoreactivity, but none contained detectable catecholamines, even after treatment with nialamide and L-DOPA [27].
• In the present study, we tested the hypothesis that norepinephrine (NE) is necessary for satiety induced by peripheral CCK-8 by using mice lacking dopamine beta-hydroxylase (Dbh(-/-)), the enzyme responsible for synthesizing NE and epinephrine from dopamine [28].
• These cells were not shown using antisera against aromatic L-amino acid decarboxylase, dopamine-beta-hydroxylase, phenylethanolamine-N-methyl-transferase, dopamine or serotonin [29].

Regulatory relationships of Dbh

• The present results show that overexpression of galanin under the control of the DBH promoter does not only occur, as expected in these mice, in noradrenline/adrenaline neurons but also in DRG neurons, particularly in large and medium-sized NPs [30].
• UCP1 messenger RNA (mRNA) and protein expression were 5-fold higher in BAT from control (Dbh+/-) compared with Dbh-/- mice [4].
• Transgenic embryos that express a constitutively active form of Ret (Ret(MEN2B)) under the control of the dopamine-beta-hydroxylase (DbetaH) promoter develop profound neuroglial hyperplasia of their sympathetic ganglia and adrenal medullae [31].
• The normal complement of neurotransmitters in noradrenergic neurons was altered by expressing the structural gene for the enzyme phenylethanolamine-N-methyltransferase (PNMT) under the control of the dopamine-beta-hydroxylase gene promoter in transgenic mice [32].
• Adrenal dopamine-beta-hydroxylase was also inhibited by NLCAs [3'O-methylnorlaudanosolinecarboxylic acid (MNLCA) Kj = 1.2 x 10(-4) M] and NLCA is a competitive inhibitor of norepinephrine methylation by hepatic catechol-O-methyltransferase (NLCA Kj = 5.6 x 10(-5) M) [33].

Other interactions of Dbh

• The in vivo developmental profile of DBH approximated that of TH [34].
• Additional triple-fluorescence experiments revealed the presence of dopamine-beta-hydroxylase immunoreactivity within 25.4 +/- 3.3% of NPY afferents to GnRH neurons [35].
• We conclude from this study that Arix and NBPhox exhibit indistinguishable and independent transcriptional regulatory properties on the DBH promoter [19].
• In the dorsal horn of the spinal cord, no differences were detected between GalOE-DBH and WT mice, both displaying a strong galanin-positive neuropil in the superficial laminae of the dorsal horn, but the transgenic mice showed a more abundant galanin-positive innervation of the ventral horn [30].
• Levels of TH, DBH, and PNMT mRNA were determined by reverse transcription-polymerase chain reaction (RT-PCR) [36].

Analytical, diagnostic and therapeutic context of Dbh

• In females, immobilization failed to induce adrenal DBH in the c-Fos-deficient mice [37].
• By the use of light microscopic (LM) immunohistochemistry, the presence of peptides and of dopamine beta-hydroxylase (DBH) in nerves supplying mammalian (guinea pig, rat, cat, pig, mouse, human) lymph nodes were examined [38].
• Western blots of sea pansy extracts revealed a protein band that co-migrated with dopamine-beta-hydroxylase (DBH) from mouse adrenal glands [39].
• To investigate this, we use gene targeting to produce mice lacking dopamine beta-hydroxylase and therefore unable to synthesize noradrenaline or adrenaline [11].
• At 2 weeks after chronic constriction injury (CCI) of the sciatic nerve, a remarkable increase in tyrosine-hydroxylase (TH) and dopamine beta-hydroxylase (DbetaH) immunoreactive (IR) axonal terminals was observed in the ipsilateral L4-L6 dorsal horn [40].

References