Expression profiling of the superior temporal gyrus of six autistic subjects and matched controls revealed differential expression of the GADD45B gene (Garbett et al., 2008). Knockdown of GADD45B in mice and rats resulted in altered long-term contextual fear conditioning and altered juvenile social behaviors, respectively (Leach et al., 2012; Kigar et al., 2015). A de novo missense variant in this gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014).
Molecular Function
This gene is a member of a group of genes that respond to environmental stresses by mediating activation of the p38/JNK pathway via binding and activation of MTK1/MEKK4 kinase, which is an upstream activator of both p38 and JNK MAPKs. The function of these genes or their protein products is involved in the regulation of growth and apoptosis.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Immune transcriptome alterations in the temporal cortex of subjects with autism.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Bilateral infusion of 1 L (100 M) Gadd45b siRNA in amygdala of P0 rat.
Allele Type: Targeted (Knock Down)
Strain of Origin: Not Specified
Genetic Background: Sprague Dawley
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Charles River
Description: Decreased time in social chamber, no change in non-social chamber or middle chamber. No change in number of exits or entries into social chamber.
Exp Paradigm: Three-chamber social approach test
Description: At P2 and P33 there is an increase in distal Adra2a promoter methylation (CRE), but not proximal (Egr1-RE)
Exp Paradigm: Methylation-sensitive restriction enzyme assay
Description: Gadd45b 20% reduced in amygdala (P2). No reduction in hypothalamus (no spreading). No reduction in Gadd45a or Gadd45g in amygdala (specific).
Exp Paradigm: Western blot
