Cntnap4 mutant mice display augmented midbrain dopaminergic release in the nucleus accumbens, a severe and highly penetrant over-grooming behavior, elevated startle responses and abnormal PPI indexes. Furthermore, deletions involving the CNTNAP4 gene were identified in patients with ASD, ADHD, and schizophrenia (Karayannis et al., 2014).
Molecular Function
This gene product belongs to the neurexin family, members of which function in the vertebrate nervous system as cell adhesion molecules and receptors.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Cntnap4 differentially contributes to GABAergic and dopaminergic synaptic transmission.
Cntnap4 null mice have increased levels of dopamine and decreased levels of Gabaergic signaling. They show abnormal perseverative allo-grooming behavior and impaired sensorimotor gating.
References
Type
Title
Author, Year
Primary
Cntnap4 differentially contributes to GABAergic and dopaminergic synaptic transmission.
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
The targeting vector was designed to replace 585 bp of the first exon of the gene and contained an inframe eEGFP followed by a new gene. Correctly targeted ES cell lines were used to produce chimaeric mice that were in turn mated with ICR females. This line was backcrossed only once with ICR after germline transmission and then was intercrossed in the following generations.
Allele Type: Strain of Origin: 129SvJ
Genetic Background: ICR*129S1
ES Cell Line: R1
Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
The targeting vector was designed to replace 585 bp of the first exon of the gene and contained an inframe eEGFP followed by a new gene. Correctly targeted ES cell lines were used to produce chimaeric mice that were in turn mated with ICR females. This line was backcrossed only once with ICR after germline transmission and then was intercrossed in the following generations.
Allele Type: Strain of Origin: 129SvJ
Genetic Background: 129S1 (Inbred)
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
The targeting vector was designed to replace 585 bp of the first exon of the gene and contained an inframe eEGFP followed by a new gene. Correctly targeted ES cell lines were used to produce chimaeric mice that were in turn mated with ICR females. This line was backcrossed for 5 generations with ICR after germline transmission and then was intercrossed in the following generations.
Allele Type: Strain of Origin: 129SvJ
Genetic Background: ICR (outbred)
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
The Cntnap4 homozygous (inbred) mice were crossed with parvalbumin-cre:red flourescent protein(RFP) background to enable targeted physiological recordings.
Allele Type: Strain of Origin: 129SvJ
Genetic Background: 129S1 (Inbred) ( and others)
ES Cell Line: Mutant ES Cell Line: Model Source:
Description: There was slight increase in the concentration of released dopamine in the caudate putamen in cntnap4 hets
Exp Paradigm: Fast scan cyclic voltammetry was used to monitor axonal dopamine spillover in the caudate putamen and nucleus accumbens. single and 20 pulse trains were used
Description: There was a significant increase in the extracellular concentration of dopamine in the nucleus accumbens in cntnap4 hets
Exp Paradigm: Fast scan cyclic voltammetry was used to monitor axonal dopamine spillover in the caudate putamen and nucleus accumbens.the significant difference was seen at 20 pulse trains used to evoke dopamine release.
Decay kinetics of miniature post synaptic currents1
Abnormal
Description: As two types of parvalbumin (pv)positive basket cells exist in the cntnap4, mutants and cntnap4 positive, both were used to study decay kinetic in paired cell recordings, with pv paired to excitatory neurons.. the pv+ and cntnap4+ had normal decay kinetics, whereas the cntnap4-ve have longer decay values and rise times
Exp Paradigm: Paired cells recordings were from pv positive interneurons connected to excitatory neurons
Description: Cntnap4 hets show increased grooming of offspring leading to significant loss of fur and whiskers in preweaning mice. however, the wt littermates do not show increased self grooming after being separated. this effect is visible only when atleast one mutant allele exists in the cage and only in the inbred strain
Exp Paradigm: NA
Description: Cntnap4 hets show increased self grooming to the point where there is significant loss of fur and almost complete loss of whiskers. this is seen only in mutants that have been inbred
Exp Paradigm: NA
Description: There was slight increase in the concentration of released dopamine in the caudate putamen in cntnap4 kos
Exp Paradigm: Fast scan cyclic voltammetry was used to monitor axonal dopamine spillover in the caudate putamen and nucleus accumbens. single and 20 pulse trains were used
Description: There was a significant increase in the extracellular concentration of dopamine in the nucleus accumbens in cntnap4 kos
Exp Paradigm: Fast scan cyclic voltammetry was used to monitor axonal dopamine spillover in the caudate putamen and nucleus accumbens.the significant difference was seen at 20 pulse trains used to evoke dopamine release.
Description: Cntnap4 kos show increased self grooming to the point where there is significant loss of fur and almost complete loss of whiskers. this is seen only in mutants that have been inbred
Exp Paradigm: NA
Description: Cntnap4 kos show increased grooming of offspring leading to significant loss of fur and whiskers in preweaning mice. however, the wt littermates do not show increased self grooming after being separated. this effect is visible only when atleast one mutant allele exists in the cage and only in the inbred strain
Exp Paradigm: NA
Description: There was a significant increase in the extracellular concentration of dopamine in the nucleus accumbens in cntnap4 kos, even in the outbred background
Exp Paradigm: Fast scan cyclic voltammetry was used to monitor axonal dopamine spillover in the caudate putamen and nucleus accumbens.the significant difference was seen at 20 pulse trains used to evoke dopamine release.
Description: Cntnap4 ko mice showed increased lfp spikes under deep anaesthesia, this was not seen in wild type controls. this difference may not have been satistically significant
Exp Paradigm: NA
