Source 1primary paper2011Journal of Neuroscience
Toolkit/dominant-negative mutant of DVL
dominant-negative mutant of DVL
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
By using viral-mediated gene transfer to overexpress a dominant-negative mutant of DVL in NAc... we show that blockade of DVL function renders mice more susceptible to social defeat stress
Usefulness & Problems
Why this is useful
This construct is used to block DVL function in the nucleus accumbens. The abstract reports that its overexpression increases susceptibility to social defeat stress and promotes depression-like behavior.; blocking DVL function in nucleus accumbens; testing causal contribution of DVL signaling to stress susceptibility
Source:
This construct is used to block DVL function in the nucleus accumbens. The abstract reports that its overexpression increases susceptibility to social defeat stress and promotes depression-like behavior.
Source:
blocking DVL function in nucleus accumbens
Source:
testing causal contribution of DVL signaling to stress susceptibility
Problem solved
It enables causal testing of whether reduced DVL signaling contributes to stress susceptibility.; provides a genetic perturbation strategy to inhibit DVL signaling in vivo
Source:
It enables causal testing of whether reduced DVL signaling contributes to stress susceptibility.
Source:
provides a genetic perturbation strategy to inhibit DVL signaling in vivo
Problem links
provides a genetic perturbation strategy to inhibit DVL signaling in vivo
LiteratureIt enables causal testing of whether reduced DVL signaling contributes to stress susceptibility.
Source:
It enables causal testing of whether reduced DVL signaling contributes to stress susceptibility.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A reusable architecture pattern for arranging parts into an engineered system.
Techniques
Functional AssayTarget processes
recombinationImplementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationoperating role: regulator
It requires a gene transfer method for expression in the nucleus accumbens, reported here as viral-mediated delivery.; requires viral-mediated expression in nucleus accumbens
The abstract does not establish isoform specificity, molecular design details, or whether the construct avoids off-target pathway effects.; specific mutant design is not described in the abstract; cell-type specificity is not described in the abstract
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Blocking DVL function in nucleus accumbens by dominant-negative DVL overexpression or pharmacological inhibition increases susceptibility to social defeat stress and promotes depression-like behavior.
By using viral-mediated gene transfer to overexpress a dominant-negative mutant of DVL in NAc, or by using a pharmacological inhibitor of DVL administered into this brain region, we show that blockade of DVL function renders mice more susceptible to social defeat stress and promotes depression-like behavior in other assays.
Overexpressing GSK3β in nucleus accumbens induces prodepression-like effects, whereas overexpressing a dominant-negative mutant of GSK3β promotes resilience to social defeat stress.
Similar prodepression-like effects were induced upon overexpressing GSK3β in the NAc, while overexpressing a dominant-negative mutant of GSK3β promoted resilience to social defeat stress.
Approval Evidence
1 source1 linked approval claimfirst-pass slug dominant-negative-mutant-of-dvl
By using viral-mediated gene transfer to overexpress a dominant-negative mutant of DVL in NAc... we show that blockade of DVL function renders mice more susceptible to social defeat stress
Source:
causal perturbationsupports
Blocking DVL function in nucleus accumbens by dominant-negative DVL overexpression or pharmacological inhibition increases susceptibility to social defeat stress and promotes depression-like behavior.
By using viral-mediated gene transfer to overexpress a dominant-negative mutant of DVL in NAc, or by using a pharmacological inhibitor of DVL administered into this brain region, we show that blockade of DVL function renders mice more susceptible to social defeat stress and promotes depression-like behavior in other assays.
Source:
Comparisons
Source-stated alternatives
The paper also uses a pharmacological inhibitor of DVL to block DVL function.
Source:
The paper also uses a pharmacological inhibitor of DVL to block DVL function.
Source-backed strengths
causally links reduced DVL function to susceptibility-related behavioral phenotypes
Source:
causally links reduced DVL function to susceptibility-related behavioral phenotypes
Compared with HIV-1 Gag-based virus-like particles
dominant-negative mutant of DVL and HIV-1 Gag-based virus-like particles address a similar problem space because they share recombination.
Shared frame: same top-level item type; shared target processes: recombination
Compared with katA::mCherry replacement construct
dominant-negative mutant of DVL and katA::mCherry replacement construct address a similar problem space because they share recombination.
Shared frame: same top-level item type; shared target processes: recombination
Compared with NaChBac activation of PVH Gpr45 neurons
dominant-negative mutant of DVL and NaChBac activation of PVH Gpr45 neurons address a similar problem space because they share recombination.
Shared frame: same top-level item type; shared target processes: recombination
Ranked Citations
- 1.