Diabetes, Vol 49, Issue 4 555-561, Copyright © 2000 by American Diabetes Association

ARTICLES

Sex-determining region Y-related protein SOX13 is a diabetes autoantigen expressed in pancreatic islets

H Kasimiotis, MA Myers, A Argentaro, S Mertin, S Fida, T Ferraro, J Olsson, MJ Rowley and VR Harley
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia.

The SOX (sex-determining region [SRY]-type high mobility group [HMG] box) family of transcription factors play key roles in determining cell fate during organ development. In this study, we have identified a new human SOX gene, SOX13, as encoding the type 1 diabetes autoantigen, islet cell antigen 12 (ICA12). Sequence analysis showed that SOX13 belongs to the class D subgroup of SOX transcription factors, which contain a leucine zipper motif and a region rich in glutamine. SOX13 autoantibodies occurred at a significantly higher frequency among 188 people with type 1 diabetes (18%) than among 88 with type 2 diabetes (6%) or 175 healthy control subjects (4%). Deletion mapping of the antibody epitopes showed that the autoantibodies were primarily directed against an epitope requiring the majority of the protein. SOX13 RNA was detected in most human tissues, with the highest levels in the pancreas, placenta, and kidney. Immunohistochemistry on sections of human pancreas identified SOX13 in the islets of Langerhans, where staining was mostly cytoplasmic. In mouse pancreas, Sox13 was present in the nucleus and cytoplasm of beta-cells as well as other islet cell types. Recombinant SOX13 protein bound to the SOX consensus DNA motif AACAAT, and binding was inhibited by homodimer formation. These observations-along with the known molecular interactions of the closely related protein, rainbow trout Sox23-suggest that SOX13 may be activated for nuclear import and DNA binding through heterodimer formation. In conclusion, we have identified ICA12 as the putative transcription factor SOX13 and demonstrated an increased frequency of autoantibody reactivity in sera from type 1 diabetic subjects compared with type 2 diabetic and healthy control subjects.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y. Wang, S. Ristevski, and V. R. Harley SOX13 Exhibits a Distinct Spatial and Temporal Expression Pattern During Chondrogenesis, Neurogenesis, and Limb Development J. Histochem. Cytochem., December 1, 2006; 54(12): 1327 - 1333. [Abstract] [Full Text] [PDF]

				M. E. Wilson, K. Y. Yang, A. Kalousova, J. Lau, Y. Kosaka, F. C. Lynn, J. Wang, C. Mrejen, V. Episkopou, H. C. Clevers, et al. The HMG Box Transcription Factor Sox4 Contributes to the Development of the Endocrine Pancreas Diabetes, December 1, 2005; 54(12): 3402 - 3409. [Abstract] [Full Text] [PDF]

				H. Iguchi, Y. Ikeda, M. Okamura, T. Tanaka, Y. Urashima, H. Ohguchi, S. Takayasu, N. Kojima, S. Iwasaki, R. Ohashi, et al. SOX6 Attenuates Glucose-stimulated Insulin Secretion by Repressing PDX1 Transcriptional Actvity and Is Down-regulated in Hyperinsulinemic Obese Mice J. Biol. Chem., November 11, 2005; 280(45): 37669 - 37680. [Abstract] [Full Text] [PDF]

				R. Goswami, T. Mohapatra, N. Gupta, R. Rani, N. Tomar, A. Dikshit, and R. K. Sharma Parathyroid Hormone Gene Polymorphism and Sporadic Idiopathic Hypoparathyroidism J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 4840 - 4845. [Abstract] [Full Text] [PDF]

				W. E. Winter, N. Harris, and D. Schatz Immunological Markers in the Diagnosis and Prediction of Autoimmune Type 1a Diabetes Clin. Diabetes, October 1, 2002; 20(4): 183 - 191. [Abstract] [Full Text] [PDF]

				H. Hedstrand, O. Ekwall, M. J. Olsson, E. Landgren, E. H. Kemp, A. P. Weetman, J. Perheentupa, E. Husebye, J. Gustafsson, C. Betterle, et al. The Transcription Factors SOX9 and SOX10 Are Vitiligo Autoantigens in Autoimmune Polyendocrine Syndrome Type I J. Biol. Chem., September 14, 2001; 276(38): 35390 - 35395. [Abstract] [Full Text] [PDF]