Nyqvist Daniel, Mattsson Göran, Köhler Martin, Lev-Ram Varda, Andersson Arne, Carlsson Per-Ola, Nordin Astrid, Berggren Per-Olof, Jansson Leif
Department of Molecular Medicine, The Rolf Luft Center for Diabetes Research, Karolinska Institutet, Stockholm, Sweden.
J Endocrinol. 2005 Aug;186(2):333-41. doi: 10.1677/joe.1.06204.
Pancreatic islet function and glucose homeostasis have been characterized in the transgenic YC-3.0 mouse, which expresses the yellow chameleon 3.0 (YC-3.0) protein under the control of the beta-actin and the cytomegalovirus promoters. Fluorescence from the enhanced yellow fluorescent protein (EYFP), one part of the yellow chameleon protein, was used as a reporter of transgene expression. EYFP was expressed in different quantities throughout most cell types, including islet endocrine and stromal cells. No adverse effects of the transgene on animal health, growth or fertility were observed. Likewise, in vivo glucose homeostasis, mean arterial blood pressure and regional blood flow values were normal. Furthermore, the transgenic YC-3.0 mouse had a normal beta-cell volume and mass as well as glucose-stimulated insulin release in vitro, compared with the C57BL/6 control mouse. Isolated islets from YC-3.0 animals continuously expressed the transgene and reversed hyperglycemia when transplanted under the renal capsule of alloxan-diabetic nude mice. We conclude that isolated pancreatic islets from YC-3.0 animals implanted into recipients without any EYFP expression, constitute a novel and versatile model for studies of islet engraftment.
已对转基因YC - 3.0小鼠的胰岛功能和葡萄糖稳态进行了表征,该小鼠在β - 肌动蛋白和巨细胞病毒启动子的控制下表达黄色变色龙3.0(YC - 3.0)蛋白。黄色变色龙蛋白的一部分即增强型黄色荧光蛋白(EYFP)发出的荧光被用作转基因表达的报告物。EYFP在包括胰岛内分泌细胞和基质细胞在内的大多数细胞类型中均有不同程度的表达。未观察到转基因对动物健康、生长或生育能力有不利影响。同样,体内葡萄糖稳态、平均动脉血压和局部血流值均正常。此外,与C57BL/6对照小鼠相比,转基因YC - 3.0小鼠的β细胞体积和质量正常,体外葡萄糖刺激的胰岛素释放也正常。从YC - 3.0动物分离的胰岛持续表达转基因,并在移植到四氧嘧啶糖尿病裸鼠的肾包膜下时逆转高血糖。我们得出结论,植入到无任何EYFP表达受体中的来自YC - 3.0动物的分离胰岛,构成了一种用于胰岛移植研究的新型通用模型。