Glutamic Acid Decarboxylase Gene Research Articles

Ovarian Steroid Regulation of Glutamic Acid Decarboxylase Gene Expression in Individual Hypothalamic Nuclei

Abstract The possibility that steroids exert their effects on luteinizing hormone (LH) and prolactin release and female sexual behaviour via altering gamma-aminobutyric acid (GABA) synthesis within the hypothalamus was investigated. Ovariectomized rats were treated with either oil, 5 mug oestradiol benzoate (OB) or 5 mug OB plus 0.5 mg progesterone (P) 48 h later; autopsy was carried out 54 h after the OB injection. At this time, both steroid treatments stimulated prolactin release and lordotic activity. OB alone exerted a negative feedback effect on LH release while OB plus P stimulated an LH surge. The brains of the rats in these three treatment groups were microdissected and glutamic acid decarboxylase messenger nbonucleic acid (GAD mRNA) was estimated in specific hypothalamic areas obtained from individual brains; these areas included the preoptic area (POA), ventromedial nucleus (VMN), anterior medial portion of the zona incerta (Zl) and the arcuatemedian eminence area (ARC/ME). GAD mRNA concentrations were assessed by the slot-blotting technique and expressed as a ratio of GAD mRNA: beta-actin mRNA. Both steroid treatments significantly reduced GAD mRNA in the ARC/ME and Zl and OB plus P also reduced the concentration in the POA, while OB alone had no effect in this area. Neither treatment affected GAD mRNA in the VMN. These results indicate that when steroids stimulate LH and prolactin release and female sexual behaviour, they reduce GABA activity probably by reducing GABA synthesis in the POA, Zl and ARC/ME. This suggests that GABA normally has an inhibitory influence on these parameters. GABA synthesis does not however, appear to be involved in the negative feedback effects of steroids on LH release as measured 54 h after OB treatment.

Sequences homologous to glutamic acid decarboxylase cDNA are present on mouse chromosomes 2 and 10

The chromosomal locations of mouse DNA sequences homologous to a feline cDNA clone encoding glutamic acid decarboxylase (GAD) were determined. Although cats and humans are thought to have only one gene for GAD, GAD cDNA sequences hybridize to two distinct chromosomal loci in the mouse, chromosomes 2 and 10. The chromosomal assignment of sequences homologous to GAD cDNA was determined by Southern hybridization analysis using DNA from mousehamster hybrid cells. Mouse genomic sequences homologous to GAD cDNA were isolated and used to determine that GAD is encoded by a locus on mouse chromosome 2 ( Gad-1) and that an apparent pseudogene locus is on chromosome 10 ( Gad-1ps). An interspecific backcross and recombinant inbred strain sets were used to map these two loci relative to other loci on their respective chromosomes. The Gad-1 locus is part of a conserved homology between mouse chromosome 2 and the long arm of human chromosome 2.

Linkage Analysis in a Family with Dominantly Inherited Torsion Dystonia: Exclusion of the Pro-Opiomelanocortin and Glutamic Acid Decarboxylase Genes and Other Chromosomal Regions Using DNA Polymorphisms

A search for the defective gene causing torsion dystonia has been carried out in a family manifesting an autosomal dominant mode of inheritance of this movement disorder. Complete neurologic examination and establishment of lymphoblast lines have been carried out for over 50 members. Linkage analysis, using cloned DNA sequences and restriction fragment length polymorphisms, was evaluated by the LOD score method with requisite assumptions for mode of inheritance, age-of-onset and incomplete gene penetrance. Genes for pro-opiomelanocortin and glutamic acid decarboxylase, which have been implicated in the etiology of the disease in rat models, were excluded as being responsible for the disease state in this family. Other regions of the genome were also excluded using DNA probes for other genes and random "unique" sequences.