| First Author | Leiter EH | Year | 2007 |
| Journal | Diabetes Obes Metab | Volume | 9 Suppl 2 |
| Pages | 14-22 | PubMed ID | 17919174 |
| Mgi Jnum | J:127015 | Mgi Id | MGI:3762571 |
| Doi | 10.1111/j.1463-1326.2007.00770.x | Citation | Leiter EH, et al. (2007) Unexpected functional consequences of xenogeneic transgene expression in beta-cells of NOD mice. Diabetes Obes Metab 9 Suppl 2:14-22 |
| abstractText | 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. |
