Ignet

Gene Information

Gene symbol: GAD2

Gene name: glutamate decarboxylase 2 (pancreatic islets and brain, 65kDa)

HGNC ID: 4093

Synonyms: GAD65

Related Genes

#	Gene Symbol	Number of hits
1	CD4	1 hits
2	CD79A	1 hits
3	CD8A	1 hits
4	GAD1	1 hits
5	IDDM2	1 hits
6	IFNG	1 hits
7	IL10	1 hits
8	IL1B	1 hits
9	IL4	1 hits
10	INS	1 hits
11	NPY	1 hits
12	PTPRN	1 hits
13	SMCR	1 hits
14	TGFB1	1 hits
15	TNF	1 hits
16	TXN	1 hits

Related Sentences

#	PMID	Sentence
1	7505244	When the various sera were tested with the GAD65 and GAD67 isoforms, produced separately by transient expression in COS cells, the enzymatic activity of GAD65 was inhibited by sera from patients with SMS and APS I, whereas no effect on the GAD67 activity was observed.
2	7519242	All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients.
3	7519242	Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots.
4	7519242	The greater magnitude and distinct specificity of the humoral response to GAD65 in SMS may reflect a biased involvement of the T helper cell type 2 (Th2) subset of CD4+ T cells and antibody responses, whereas IDDM is likely mediated by the Th1 subset of CD4+ T cells and cytotoxic T cell responses.
5	8034738	In this study we have investigated the targeting signal of the 65-kD isoform of glutamic acid decarboxylase (GAD65), a major autoantigen in two autoimmune diseases: Stiff-Man syndrome and insulin-dependent diabetes mellitus.
6	7523207	Peptide antibodies to the P2-C protein, GAD65, and GAD67 were raised to analyze their immunoreactivity by enzyme-linked immunosorbent assay and immunoblotting with GAD purified from the brain and pancreas of mice that develop hyperglycemia after the infection.
7	7523207	All three peptide antisera reacted very strongly with homologous peptides; P2-C antiserum cross-reacted with GAD65 as efficiently as GAD65 antiserum with P2-C, but no cross-reaction was detected between P2-C and GAD67 although cross-reaction between the two GADs was quite pronounced.
8	7523207	The immunoreactivity of the mouse and IDDM sera to P2-C and GAD65 peptides was blocked by pre-adsorption with mouse GAD.
9	7833679	Conversely, CD8+ cells from patients with IDDM are activated normally in response to TSHR, but significantly less to GAD-65.
10	7772701	We determined antibodies against human recombinant GAD in Japanese diabetic patients using a radioimmunoassay with competition between in vitro translated 35S-GAD65 and non-labelled recombinant human GAD65 (rhGAD65).
11	7532143	Since the GAD67 isoform is highly homologous to GAD65 but is usually not a target of the GAD autoantibodies in IDDM sera, we created six GAD65/GAD67 chimeric proteins to maintain the overall GAD protein conformation and used these chimeric proteins to map conformation-dependent epitopes of GAD65 targeted by IDDM sera.
12	7532143	We find that the GAD binding present in most IDDM sera (n = 11 of 12) is composed of two distinct GAD antibody specificities that target different conformation-dependent regions of the GAD65 protein, one that is located between amino acids 240 and 435 (termed IDDM-E1) and one that is located between amino acids 451 and 570 (termed IDDM-E2).
13	7532577	Glutamic acid decarboxylase (GAD), a target of both autoantibodies and autoreactive T-cells in insulin-dependent diabetes (IDD), exists as two homologous forms, GAD65 and GAD67.
14	7532577	GAD65 is preferentially expressed in human islets and recognized by autoantibodies in IDD, but which form primarily elicits GAD autoimmunity is unknown.
15	7822765	Differential expression of GAD isoforms within islet alpha- and beta-cells supports the role of GAD65 in autoimmune diabetes and stiff-man syndrome.
16	8781713	Since glutamic acid decarboxylase-65 (GAD-65) is a target autoantigen in IDDM, we investigated whether the cytokines IL-1 beta, TNF alpha IFN gamma altered islet cell expression of GAD-65 and whether the effect of cytokines on GAD-65 expression was similar to their effect on insulin secretion.
17	8781713	We found that: 1) IL-1 beta at low dose (1 U/ml) which stimulated insulin secretion, had no effect on GAD-65 expression, whereas higher doses of IL-1 beta (10, 100, 1000 U/ml) which inhibited insulin secretion, decreased GAD-65 expression. 2) TNF alpha at doses of 10, 100, 1000 U/ml which stimulated insulin secretion had no effect on GAD-65 expression. 3) IFN gamma at doses of 10, 100, 1000 U/ml had no effect on insulin secretion or on GAD-65 expression. 4) In combination, IL-1 beta plus TNF alpha and IFN gamma showed a similar inhibitory effect on GAD-65 expression as IL-1 beta alone.
18	8781713	In summary: 1) IL-1 beta dramatically inhibits GAD-65 expression. 2) TNF alpha and IFN gamma have no effect on GAD-65 expression.
19	8781713	Of these three cytokines, IL-1 beta is the primary cytokine affecting GAD-65 expression.
20	8666914	Consistent with the induction of an active tolerance mechanism, splenic CD4+ (but not CD8+) T cells from GAD65 peptide-treated mice, inhibited the adoptive transfer of IDDM to NOD-scid/scid mice.
21	8666914	Finally, GAD65 peptide treatment reduced insulitis and long-term IDDM incidence.
22	10814590	However, this difficulty was recently surmounted in our laboratory by expressing GAD65 as a fusion protein with thioredoxin [Papouchado, Valdez, Ghiringhelli, Poskus and Erm�cora (1997) Eur.
23	11121550	For the same purpose a truncated version of this fusion protein which contained the entire GAD65 linked to the 203 carboxy-terminal amino acids of IA-2 (GAD-dIA-2) was made.
24	11160264	This protection was GAD65-specific since NOD mice immunized with pDNA encoding hen egg lysozyme-IgGFc and IL-4 continued to develop diabetes.
25	11418698	We previously demonstrated that administration of plasmid DNAs (pDNAs) encoding IL-4 and a fragment of glutamic acid decarboxylase 65 (GAD65) fused to IgGFc induces GAD65-specific Th2 cells and prevents insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice.
26	11418698	These results demonstrate that insulin- and GAD65-specific T cell reactivity induced by pDNA vaccination has distinct effects on the progression of IDDM.
27	11905849	We have investigated recognition of the GAD65 protein, one of the well-characterized autoantigens in type I diabetes, among individuals carrying the HLA-DR4 haplotypes characteristic of susceptibility to IDDM.
28	16177033	Furthermore, increases in the GABA-synthesizing enzyme glutamic acid decarboxylase 65 (GAD65) mRNA expression preceded decreases in NPY mRNA expression in the arcuate nucleus in the cultures.
29	16177033	Experiments in vivo also demonstrated that increases in GAD65 mRNA expression in the arcuate nucleus preceded decreases in the NPY mRNA expression in a fasting-refeeding paradigm and that intracerebroventricular injection of insulin increased GAD65 mRNA expression in the arcuate nucleus in fasted rats.
30	16249070	A slightly higher percentage of diabetic subjects had GAD65(555-567) tetramer-positive T cells upon GAD65(555-567) peptide stimulation on the total CD4+ T-cell populations compared to healthy subjects.
31	17163450	In cells cultured from healthy individuals, the inclusion of autologous CD8+ T cells at physiological levels resulted in a dramatic decrease in the magnitude of in vitro CD4+ T cell responses to GAD65 peptide.
32	17163450	The suppression of CD4+ T cell responses to GAD65 in healthy individuals raises the possibility that CD8+ suppressor T cells play an important role in controlling potentially autoreactive T cells in the general population.
33	17459095	The glutamate decarboxylase gene (GAD2) encodes GAD65, an enzyme catalysing the production of the gamma-aminobutyric acid (GABA) which interacts with neuropeptide Y to stimulate food intake.
34	19752238	Furthermore, suppression of T1D was dependent on beta cell-specific IL-10-secreting CD4+ T cells, although the frequency of GAD65-specific FoxP3-expressing CD4+ T cells was also increased in sIA(g7)-pGAD65 dimer vaccinated NOD mice.
35	20406664	Increased anti-GAD65 IgG1, serum IgA and unchanged IgG2a antibodies titers; together with an increase of IL-4, IL-10 production and a decrease of IFN-gamma production suggested possible activation of GAD65-specific Th2 immune responses.
36	20348424	In addition, GAD65-specific CD4(+) T cells isolated from the brain were activated and produced IFN-gamma.
37	19690518	Efficacy was associated with an expansion of bystander suppressor regulatory T cells (Tregs) recognizing the C-terminal region of GAD65 and secreting interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), and interferon-gamma (IFN-gamma).