Unexpected functional consequences of xenogeneic transgene expression in ?-cells of NOD mice
| Autor: | Peter C. Reifsnyder, Edward H. Leiter, J. Driver, Alexander V. Chervonsky, S. Kamdar, Caroline Morgane Choisy-Rossi, M. Hara, D. V. Serreze |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Endocrinology Diabetes and Metabolism medicine.medical_treatment Transgene Green Fluorescent Proteins Gene Expression Cre recombinase Mice Transgenic Nod Biology Diabetes Mellitus Experimental Green fluorescent protein Mice Endocrinology Mice Inbred NOD Insulin-Secreting Cells Gene expression Internal Medicine medicine Animals Transgenes Pancreas NOD mice Integrases Insulin medicine.disease Molecular biology Diabetes Mellitus Type 1 Female Insulitis |
| Zdroj: | Diabetes, Obesity and Metabolism. 9:14-22 |
| ISSN: | 1463-1326 1462-8902 |
| DOI: | 10.1111/j.1463-1326.2007.00770.x |
| Popis: | We describe unexpected alterations in the non-obese diabetic (NOD/Lt) mouse model of type 1 diabetes (T1D) following forced beta-cell expression of non-mammalian genes ligated to an insulin promoter sequence. These include the jellyfish green fluorescent protein (GFP), useful for beta-cell identification, and the bacteriophage P1 Cre recombinase, necessary for beta cell-specific ablation of a gene using a Cre-loxP system. Homozygous expression of GFP, driven by the mouse insulin 1 gene promoter (MIP-GFP) in a single transgenic line of NOD mice, produced T1D in postnatal mice that was not associated with insulitis, but rather beta cell-depleted islets. Hemizygous transgene expression suppressed spontaneous autoimmune T1D in females, and produced a male glucose intolerance syndrome associated with age-dependent declines in plasma insulin content. Among lines of transgenic NOD/Lt mice expressing Cre recombinase driven by the rat insulin 2 promoter (RIP-Cre), high, non-mosaic expression correlated with suppressed T1D development. These findings emphasize the need for careful characterization of genetically manipulated NOD mouse stocks to insure that model characteristics have not been compromised. |
| Databáze: | OpenAIRE |
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