Cloning, Expression and Characterization of Human Autoantigens

Lan, M S.

Abstract

This project is designed to isolate genes specifically expressed by human pancreatic beta islet cells which regulate glucose metabolism and play a major role in Insulin-Dependent Type-1 Diabetes Mellitus (IDDM). Our strategy was to prepare subtraction library. Briefly, two libraries were made: one from insulinoma (beta cell tumor) and the other from glucagonoma (alpha cell tumor). Then, we subtracted the glucagonoma library from the insulinoma library. Each residual cDNA clone was screened against different RNAs isolated from various organs. Two novel cDNA clones (IG-34 and IG-134A) were selected. Double-strand sequencing of 1.5 Kb IG-34 insert showed no homology with published DNA sequence stored in GenBank. Both mouse and rat counterparts of IG-34 were also isolated by cross- hybridization with the human clone. Functional studies of IG34 expression are currently in progress.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Dental & Craniofacial Research (NIDCR)
• Type: Intramural Research (Z01)
• Project #: 1Z01DE000423-06
• Application #: 3854204
• Support Year: 6
• Fiscal Year: 1991

Institution

• Name: National Institute of Dental & Craniofacial Research
• Country: United States

Publications

Cai, Tao; Hirai, Hiroki; Fukushige, Tetsunari et al. (2009) Loss of the transcriptional repressor PAG-3/Gfi-1 results in enhanced neurosecretion that is dependent on the dense-core vesicle membrane protein IDA-1/IA-2. PLoS Genet 5:e1000447

Kim, Soo Mi; Theilig, Franziska; Qin, Yan et al. (2009) Dense-core vesicle proteins IA-2 and IA-2{beta} affect renin synthesis and secretion through the {beta}-adrenergic pathway. Am J Physiol Renal Physiol 296:F382-9

Khil, L-Y; Jun, H-S; Kwon, H et al. (2007) Human chorionic gonadotropin is an immune modulator and can prevent autoimmune diabetes in NOD mice. Diabetologia 50:2147-55

Notkins, Abner Louis (2007) New predictors of disease. Molecules called predictive autoantibodies appear in the blood years before people show symptoms of various disorders. Tests that detected these molecules could warn of the need to take preventive action. Sci Am 296:72-9

Mett, Vadim; Shamloul, Abdel-Moneim; Hirai, Hiroki et al. (2007) Engineering and expression of the intracellular domain of insulinoma-associated tyrosine phosphatase (IA-2ic), a type 1 diabetes autoantigen, in plants. Transgenic Res 16:77-84

Harashima, S-I; Harashima, C; Nishimura, T et al. (2007) Overexpression of the autoantigen IA-2 puts beta cells into a pre-apoptotic state: autoantigen-induced, but non-autoimmune-mediated, tissue destruction. Clin Exp Immunol 150:49-60

Li, Na; Shigihara, Toshikatsu; Tzioufas, Athanasios G et al. (2007) Human chorionic gonadotropin prevents Sjogren's syndrome-like exocrinopathy in mice. Arthritis Rheum 56:2211-5

Kubosaki, Atsutaka; Nakamura, Shinichiro; Clark, Anne et al. (2006) Disruption of the transmembrane dense core vesicle proteins IA-2 and IA-2beta causes female infertility. Endocrinology 147:811-5

Harashima, Shin-ichi; Clark, Anne; Christie, Michael R et al. (2005) The dense core transmembrane vesicle protein IA-2 is a regulator of vesicle number and insulin secretion. Proc Natl Acad Sci U S A 102:8704-9

Kubosaki, Atsutaka; Nakamura, Shinichiro; Notkins, Abner Louis (2005) Dense core vesicle proteins IA-2 and IA-2beta: metabolic alterations in double knockout mice. Diabetes 54 Suppl 2:S46-51