A DRD1 haplotype was found to be associated with risk for autism spectrum disorders in male-only affected sib-pair families (Hettinger et al., 2008).
Molecular Function
This gene encodes the D1 subtype of the dopamine receptor, the most abundant dopamine receptor in the central nervous system. This G-protein coupled receptor stimulates adenylyl cyclase and activates cyclic AMP-dependent protein kinases. D1 receptors regulate neuronal growth and development, mediate some behavioral responses, and modulate dopamine receptor D2-mediated events
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References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
A DRD1 haplotype is associated with risk for autism spectrum disorders in male-only affected sib-pair families.
Drd1 l null mice have impaired fear conditioning memory and eye-blink conditioning, along lack of long-term potantiation in CA1-CA3 synapses of the hippocampus.
References
Type
Title
Author, Year
Primary
Associative learning and CA3-CA1 synaptic plasticity are impaired in D1R null, Drd1a-/- mice and in hippocampal siRNA silenced Drd1a mice.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
A PGK-neomycin based targeting vector replaced the 95% of the coding region.
Allele Type: Targeted (Knock-out)
Strain of Origin: 129P2/OlaHsd
Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
Wild type C57BL/6 mice were treated with lenti-Drd1a-silencer RNA.They were targeted to different regions in the Drd1a RNA.
Allele Type: Strain of Origin: Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source:
Description: No ltp was generated in drd1a nullizygous mice at the ca3-ca1 synapse. whereas in wt controls >200% of baseline values after hfs.
Exp Paradigm: Ltp was measured in the ca3-ca1 ciruits, after hfs of schaffer collaterals
Description: The slopes of evoked fepsps in the drd1a nullizygous mice was significantly smaller than in corresponding control animals. this shows a a decline in activity- dependent increases in synaptic efficiency
Exp Paradigm: Electrical stimulation of schaffer collaterals was carried out during the classical eye blink conditioning paradigm, during the habituation and conditioning session, after the cs presentation
Cued or contextual fear conditioning: memory of cue1
Decreased
Description: Wild type mice had significantly higher levels of freezing than drd1a-/- when reexposed to the training context. wt also showed increased freezing in a new context than the nullizygous mice, when the conditioned stimulus was presented in the new context.
Exp Paradigm: On the training day mice were placed in the conditioning chamber for 2 min before the onset of the cs, a tone, during the last two seconds of the tone, the us - electric shock of 0.7 ma was presented. conditioning was tested in the same chamber by measuring freezing behavior.
Cued or contextual fear conditioning: memory of cue1
Decreased
Description: Drd1a-/- nullizygous mice were unable to learn the avoidance response in first 2 days of training, unlike the wild type. the demonstrated significant impairment in avoidance training. no reduction in crossing latency was seen.
Exp Paradigm: A two way shuttle box was used, with crossing into any of the compartments possible. each trial consisted of a tone presented for 10s in the compartment a mouse stayed ( after the initial 3 min period of exploration). after 5 s of the tone (conditioned stimulus) an electric shock was provided to the foot . crossing while the shock was being delivered were considered escape responsed. response 'crossing latencies' were counted as the time from the onset of cs until the animal crossed into the opposite compartment
Description: Drd1a nullizygous mice did not show any reduction in escape latency in the barnes maze even after 11 days of training, whereas by the seventh day of training wild type mice had reached the minimum latency.
Exp Paradigm: Mice are trained daily for 11 days to escape the maze, followed by the probe trial, 3 days after the training period. the apparatus is an open field to escape the field to a black escape box.
Cued or contextual fear conditioning: memory of cue1
Decreased
Description: Drd1a-/- nullizygous mice exhibit signitificantly shorter latencies to cross into the black box, indicating reduced memory strength, than wild type mice, even after foot shocks were given at higher intensities above pain threshold.
Exp Paradigm: Mice were placed in a box that had one dark, black and one illuminated white compartment. if the mouse crossed over to the black compartment the door closed and the mouse received a shock.
Description: The % conditioned response (cr) increased significantly across conditioning sessions in the wt controls, however neither the drd1a nullizygous not the drd1a-sirna mice showed increase in crs.
Exp Paradigm: Three animals were placed in separate small plastic chambers. a tone was presented as the cs, the us consisted of a cathodal, square pulse applied to the supraorbital nerve, 500 ms after the end of the cs. a total of two habituation and 10 conditioning sessions were performed for each animal.60 cs-us presentations in one conditioning session. for observation of the conditioned response (cr), the cs was presented alone in 10% of the cases.
Description: Basal expression of egr1/zif268 was similar in the hippocampi of drd1a nullizygous animals and drd1a-sirna mice to their respective wt controls. however 24 h after in vivo tetanic stimulation of ca3 cell layer, egr1 expression increased significantly in the hippocampus of wt and wt-gfp animals, compared to non stimulated wt and wt-gfp animals. however, in the drd1a nullizygous animals and in drd1a-sirna animals, this induction of egr1 expression was not seen or was inhibited.
Exp Paradigm: Gene regulation
Description: No ltp was generated in drd1a nullizygous mice or in drd1a-sirna mice at the ca3-ca1 synapse. whereas in wt controls >200% of baseline values after hfs.
Exp Paradigm: Ltp was measured in the ca3-ca1 ciruits, after hfs of schaffer collaterals
Description: The slopes of evoked fepsps in the drd1a nullizygous mice and the drd1a-sirna mice was significantly smaller than in corresponding control animals. this shows a a decline in activity dependent increases in synaptic efficiency
Exp Paradigm: Electrical stimulation of schaffer collaterals was carried out during the classical eye blink conditioning paradigm, during the habituation and conditioning session, after the cs presentation
Description: Drd1a null mice and drd1a-sirna mice showed no increase in crs, whereas, the % conditioned response (cr) increased significantly across conditioning sessions in the wt controls
Exp Paradigm: Three animals were placed in separate small plastic chambers. a tone was presented as the cs, the us consisted of a cathodal, square pulse applied to the supraorbital nerve, 500 ms after the end of the cs. a total of two habituation and 10 conditioning sessions were performed for each animal.60 cs-us presentations in one conditioning session. for observation of the conditioned response (cr), the cs was presented alone in 10% of the cases.
Description: 24 h after in vivo tetanic stimulation of ca3 cell layer, egr1 expression increased significantly in the hippocampus of wt and wt-gfp animals, compared to non stimulated wt and wt-gfp animals. however, in the drd1a nullizygous animals and in drd1a-sirna animals, this induction of egr1 expression was not seen. basal expression of egr1/zif268 was similar in the hippocampi of drd1a nullizygous animals and drd1a-sirna mice to their respective wt controls.
Exp Paradigm: Gene regulation
