Abnormal expression levels of GAD1 mRNA have previously been observed in cerebellar Purkinje cells and cerebellar interneurons in ASD cases (Yip et al., 2007; Yip et al., 2008). More recently, male GAD1 haploinsufficient mice were reported to have impaired social behavior (Sandhu et al., 2014).
Molecular Function
This gene encodes an enzyme that catalyzes the production of GABA. Mutations in this gene are associated with cerebral palsy, spastic quadriplegic 1 (CPSQ1) [MIM:603513].
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Decreased GAD67 mRNA levels in cerebellar Purkinje cells in autism: pathophysiological implications.
Gad1 KO mice die at birth with cleft palate and apnea. They have decreased levels of glutamic acid decarboxylase and gamma-aminobutyric acid in the cerebral cortex.
References
Type
Title
Author, Year
Additional
Glutamic acid decarboxylase 67 haplodeficiency impairs social behavior in mice.
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
A c-DNA coding enhanced GFP was targeted to the locus encoding GAD67. Chimeras were generated using the positive ES cells and bred in the C57BL/6 background. Backcrossed to C57BL/6ola for 12 generations and maintained as hets.
Allele Type: Targeted (reporter)
Strain of Origin: C57BL/6NCrlj x CBA/JNCrlj
Genetic Background: C57BL/6Ola
ES Cell Line: TT2
Mutant ES Cell Line: Model Source:
Circadian rhythms: timing/phases of locomotor activity1
Decreased
Description: Gad1 het mice display a shift in phase, by 2 h, in activity. wild type mice showed a shift from inactive to active 1 h preceding lights off and from active to inactive at 1 h preceding lights on. whereas gad1 hets shifted from inactive to active 1 h after lights off and active to inactive 1 h after lights on.
Exp Paradigm: The phase at which active to inactive ( in the morning or lights on) and inactive to active ( in the night, lights off) were recorded
Description: Gad1 het mice showed a reduced latency for the first mounting of an unfamiliar male intruder mouse and also a trend towards increased number of mountings
Exp Paradigm: NA
Neuronal activation following behavioral stimulation: c-fos levels1
Decreased
Description: Gad1 het mice had significant reduction in c-fos labeling in the medial and cortical amygdala compared to wild type littermates
Exp Paradigm: Measurement of c-fos levels in the brain: amygdala, after social behavior testing
Neuronal activation following behavioral stimulation: c-fos levels1
Decreased
Description: Gad1 het mice had significant reduction in c-fos labeling in the lateral septum, stria terminalis and medial preoptic area compared to wild type littermates
Exp Paradigm: NA
Description: Gad1 het mice show decreased sensitivity to non social and social olfactory cues when the cue was diluted. wild type littermates showed a preference for all rose odor dilutions and all social odor dilutions
Exp Paradigm: 10000 and 100 fold dilutions for the rose essence and 100 fold and 10 fold dilutions of female urine sample were used in the odor test, where bedding is tagged with only one or the other.
Description: Gad1 het mice did not prefer pr spend more time exploring female soiled bedding over male soiled bedding, contrasting the behavior or wild type littermates
Exp Paradigm: Preference of male versus female soiled bedding was tested in males
Description: Gad1 hets had no preference for unfamiliar female mice over unfamiliar male mice, unlike wild type littermate mice
Exp Paradigm: Contact number index was measured
Description: Gad1 het mice avoided social interaction with an unfamiliar stimulus mouse and spent more time exploring an empty tube compared to an unfamiliar mouse
Exp Paradigm: Number of vsits to the interaction partner were counted
Description: Gad1 het mice did not spend more time exploring the bedding soiled by unfamiliar male mice, unlike wild type littermates
Exp Paradigm: Preference of soiled bedding from an unfamiliar male and rose essence was tested.
Description: Gad1 het mice had decreased incidence of attacking intruder mice and a higher incidence of being chased by the intruder mice
Exp Paradigm: NA
