Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IA-2 is a transmembrane protein tyrosine phosphatase, expressed in neuroendocrine cells, and a major autoantigen in insulin-dependent diabetes mellitus. In the present study we elucidated the structure of the IA-2 gene (HGMW-approved symbol PTPRN) and its promoter sequence. A 40-kb genomic clone covering the whole IA-2 coding sequence and 4 kb proximal 5'-upstream sequence was isolated and mapped. The IA-2 gene encompasses approximately 20 kb with 23 exons ranging from 34 bp to more than 650 bp. The extracellular domain is encoded by exons 1-12, the transmembrane region by exon 13, and the intracellular domain by exons 14-23. The transcriptional start site(s) of the IA-2 gene was mapped by 5' rapid amplification of cDNA ends to 97 bp upstream of the translational start site. A 3-kb 5'-upstream region was sequenced, revealing a GC-rich region and TATA-less sequence containing several potential transcription-regulating sites (i.e., Sp1, CREB, GATA-1, and MZF). Functional promoter activity was confirmed by transient transfection of U87MG cells with deletion mutants linked to a luciferase reporter gene.
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PMID:Genomic structure and promoter sequence of the insulin-dependent diabetes mellitus autoantigen, IA-2 (PTPRN). 982 38

Diabetes mellitus in dogs shares many characteristics with the human type 1 disease and virtually all diabetic dogs require insulin therapy to control hyperglycaemia. Insulin deficiency is suspected to result from immune-mediated destruction of pancreatic beta cells in some cases. Human patients suffering from Type 1A (immune-mediated) diabetes or latent autoimmune diabetes of the adult (LADA) demonstrate circulating autoantibodies against the 65kDa isoform of glutamic acid decarboxylase (GAD65) and/or insulinoma antigen-2 (IA-2). The aims of the current study were to develop radio-immunoassays to detect serum antibodies against recombinant canine GAD65 and IA-2 and to identify diabetic dogs showing serological evidence of autoreactivity to these pancreatic beta cell antigens. Canine GAD65 and the 3' end of IA-2 (coding for amino acids 771-979 of the intracellular domain) were amplified by PCR from cDNA prepared from canine insulinoma tissue and cloned into the pCRII vector. The canine sequences were later confirmed by identifying GAD2 and PTPRN genes from the dog genome assembly. Recombinant (35)S-methionine-radiolabelled canine GAD65 and IA-2 (771-979) proteins were used in radio-immunoprecipitation assays to screen sera from 30 newly diagnosed diabetic dogs and 30 control dogs. Four of 30 canine diabetic patients had significant GAD65 autoreactivity (p<0.01) compared to controls and 3 dogs were positive for autoantibodies to IA-2 (771-979). Two diabetic dogs showed dual autoantigen reactivity. These preliminary data indicate that serological reactivity to GAD65 and IA-2 is present in a proportion of diabetic dogs and suggests that, in some cases, canine diabetes is associated with an autoimmune response to these antigens.
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PMID:Autoantibodies to GAD65 and IA-2 in canine diabetes mellitus. 1870 2