The proximal islet-specific glucose-6-phosphatase catalytic subunit-related protein autoantigen promoter is sufficient to initiate but not maintain transgene expression in mouse islets in vivo.

Frigeri C, Martin CC, Svitek CA, Oeser JK, Hutton JC, Gannon M, O'Brien RM
Diabetes. 2004 53 (7): 1754-64

PMID: 15220199

We have previously reported the discovery of an islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) that is predominantly expressed in islet beta-cells. IGRP has recently been identified as a major autoantigen in a mouse model of type 1 diabetes. The analysis of IGRP-chloramphenicol acetyltransferase (CAT) fusion gene expression in transiently transfected islet-derived hamster insulinoma tumor and betaTC-3 cells revealed that the promoter region located between -306 and +3 confers high-level reporter gene expression. To determine whether this same promoter region is sufficient to confer islet beta-cell-specific gene expression in vivo, it was ligated to a beta-galactosidase reporter gene, and transgenic mice expressing the resulting fusion gene were generated. In two independent founder lines, this -306 to +3 promoter region was sufficient to drive beta-galactosidase expression in newborn mouse islets, predominantly in beta-cells, which was initiated during the expected time in development, around embryonic day 12.5. However, unlike the endogenous IGRP gene, beta-galactosidase expression was also detected in the cerebellum. Moreover, beta-galactosidase expression was almost completely absent in adult mouse islets, suggesting that cis-acting elements elsewhere in the IGRP gene are required for determining appropriate IGRP tissue-specific expression and for the maintenance of IGRP gene expression in adult mice.

MeSH Terms (17)

Aging Animals Animals, Newborn Brain Cells, Cultured Gene Expression Genes, Reporter Glucose-6-Phosphatase Homeodomain Proteins Islets of Langerhans Mice Mice, Transgenic Promoter Regions, Genetic Proteins Protein Structure, Tertiary Transcription Factors Transgenes

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