This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huang, H.-p. Articles by Tsai, M.-J. Search for Related Content PubMed PubMed Citation Articles by Huang, H.-p. Articles by Tsai, M.-J.

Neogenesis of ß-Cells in Adult BETA2/NeuroD-Deficient Mice

Department of Molecular and Cellular Biology (H.-p.H., K.C., E.N.-G., D.E., M.-J.T.), Medicine (M.-J.T.) and Program in Developmental Biology (M.-J.T.), Baylor College of Medicine, Houston Texas 77030

Address all correspondence and requests for reprints to: Ming-Jer Tsai, Ph.D., Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030. E-mail: mtsai{at}bcm.tmc.edu.

BETA2/NeuroD, a basic helix-loop-helix transcription factor, is expressed in pancreatic endocrine cells during development and regulates insulin gene expression. We demonstrated previously that the endocrine pancreas of BETA2/NeuroD-deficient mice undergoes massive apoptosis and, consequently, animals die of diabetes shortly after birth. Here we show that a significant fraction of BETA2-deficient mice in a new genetic background can survive diabetes and live to adulthood through the process of ß-cell neogenesis. Morphometric examination indicates that pancreatic ß-, but not -cell mass, was restored to a level comparable to that of wild-type animals. However, the newly formed islet cells cannot form mature islets of Langerhans, indicating an indispensable role of BETA2 in morphogenesis of normal islet structure. Furthermore, immunohistochemical examinations revealed that newly formed ß-cells of BETA2/NeuroD-deficient mice come from two sources: either directly budding from the pancreatic ductal tree or from the preexisting ß-cells in the residual endocrine pancreas. Our results indicate that ß-cell neogenesis in our BETA2/NeuroD-deficient mice contributes to their survival, and these mice may provide a useful model for studying the mechanism of ß-cell regeneration.

This article has been cited by other articles:

				D. A. Babu, S. K. Chakrabarti, J. C. Garmey, and R. G. Mirmira Pdx1 and BETA2/NeuroD1 Participate in a Transcriptional Complex That Mediates Short-range DNA Looping at the Insulin Gene J. Biol. Chem., March 28, 2008; 283(13): 8164 - 8172. [Abstract] [Full Text] [PDF]

				C.-H. Lin, S. J. Tapscott, and J. M. Olson Congenital Hypothyroidism (Cretinism) in neuroD2-Deficient Mice. Mol. Cell. Biol., June 1, 2006; 26(11): 4311 - 4315. [Abstract] [Full Text] [PDF]

				H. Hua, Y.-Q. Zhang, S. Dabernat, M. Kritzik, D. Dietz, L. Sterling, and N. Sarvetnick BMP4 Regulates Pancreatic Progenitor Cell Expansion through Id2 J. Biol. Chem., May 12, 2006; 281(19): 13574 - 13580. [Abstract] [Full Text] [PDF]

				R. Gianani, A. Putnam, T. Still, L. Yu, D. Miao, R. G. Gill, J. Beilke, P. Supon, A. Valentine, A. Iveson, et al. Initial Results of Screening of Nondiabetic Organ Donors for Expression of Islet Autoantibodies J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1855 - 1861. [Abstract] [Full Text] [PDF]

				C.-H. Lin, S. Hansen, Z. Wang, D. R. Storm, S. J. Tapscott, and J. M. Olson The dosage of the neuroD2 transcription factor regulates amygdala development and emotional learning PNAS, October 11, 2005; 102(41): 14877 - 14882. [Abstract] [Full Text] [PDF]

				K. Chu and M.-J. Tsai Neuronatin, a Downstream Target of BETA2/NeuroD1 in the Pancreas, Is Involved in Glucose-Mediated Insulin Secretion Diabetes, April 1, 2005; 54(4): 1064 - 1073. [Abstract] [Full Text] [PDF]

				R. Suzuki, K. Tobe, Y. Terauchi, K. Komeda, N. Kubota, K. Eto, T. Yamauchi, K. Azuma, H. Kaneto, T. Taguchi, et al. Pdx1 Expression in Irs2-deficient Mouse {beta}-Cells Is Regulated in a Strain-dependent Manner J. Biol. Chem., October 31, 2003; 278(44): 43691 - 43698. [Abstract] [Full Text] [PDF]

				X. Li and A. Minden Targeted Disruption of the Gene for the PAK5 Kinase in Mice Mol. Cell. Biol., October 15, 2003; 23(20): 7134 - 7142. [Abstract] [Full Text] [PDF]

				S. K. Ray, J. Nishitani, M. W. Petry, M. Y. Fessing, and A. B. Leiter Novel Transcriptional Potentiation of BETA2/NeuroD on the Secretin Gene Promoter by the DNA-Binding Protein Finb/RREB-1 Mol. Cell. Biol., January 1, 2003; 23(1): 259 - 271. [Abstract] [Full Text]

				H. Wang, K. Hagenfeldt-Johansson, L. A. Otten, B. R. Gauthier, P. L. Herrera, and C. B. Wollheim Experimental Models of Transcription Factor-Associated Maturity-Onset Diabetes of the Young Diabetes, December 1, 2002; 51(90003): S333 - 342. [Abstract] [Full Text] [PDF]