Van der Ven L T, Roholl P J, Reijnen-Gresnigt M G, Bloemen R J, van Buul-Offers S C
Department of Paediatrics, Wilhelmina Children's Hospital, University of Utrecht, The Netherlands.
Histochem Cell Biol. 1997 Mar;107(3):193-203. doi: 10.1007/s004180050104.
Previously, transgenic mice were constructed overexpressing human insulin-like growth factor II (IGF-II) under control of the H2kb promoter. The IGF-II transgene was highly expressed in thymus and spleen, and these organs showed an increase in weight. In the current study we have analyzed the sites of IGF-II mRNA expression, the distribution of IGF-II, IGF-I, and both IGF receptors, and histomorphometrical changes in thymus and spleen. With in situ mRNA hybridization, expression of the IGF-II transgene is found with high intensity in the thymic medulla and in the white pulp/marginal zone of the spleen, whereas there were scattered positive cells in the thymic cortex and in the splenic red pulp. Hybridization was restricted to non-lymphocytic cells. Immunohistochemistry revealed intense IGF-II peptide staining with the same distribution as IGF-II mRNA. There was additional intense IGF-II staining of all elements in the splenic red pulp (including trabeculae) and diffuse, low level staining in the thymic cortex. These findings were not observed in control mice. In the thymic medulla, most IGF-II producing cells co-labelled with keratin, whereas a minor population also stained for the monocyte/ macrophage marker MOMA-2. In the spleen, co-labelling of IGF-II producing cells was found with MOMA-1 (marginal zone), or with the dendritic cell marker NLDC-145 (red pulp). IGF-I and both IGF receptors were found in these organs in nearly all cell types, with a similar pattern in transgenic mice and in control animals. Histomorphometric analysis revealed a marked increase of thymus cortex size and an increased trabecular size in the spleen. This suggests that IGF-II overproduction induces local effects (auto/paracrine) in the thymic cortex, but not in the thymic medulla. Trabecular growth in the spleen most likely is a distant effect (paracrine or endocrine) of IGF-II overproduction.
先前构建了在H2kb启动子控制下过表达人胰岛素样生长因子II（IGF-II）的转基因小鼠。IGF-II转基因在胸腺和脾脏中高度表达，且这些器官重量增加。在本研究中，我们分析了IGF-II mRNA的表达位点、IGF-II、IGF-I以及两种IGF受体的分布，以及胸腺和脾脏的组织形态计量学变化。通过原位mRNA杂交发现，IGF-II转基因在胸腺髓质以及脾脏白髓/边缘区有高强度表达，而在胸腺皮质和脾脏红髓中有散在的阳性细胞。杂交仅限于非淋巴细胞。免疫组织化学显示IGF-II肽染色强烈，其分布与IGF-II mRNA相同。脾脏红髓中的所有成分（包括小梁）也有强烈的IGF-II染色，胸腺皮质中有弥漫性低水平染色。在对照小鼠中未观察到这些发现。在胸腺髓质中，大多数产生IGF-II的细胞与角蛋白共标记，而少数细胞也表达单核细胞/巨噬细胞标志物MOMA-2。在脾脏中，发现产生IGF-II的细胞与MOMA-1（边缘区）或树突状细胞标志物NLDC-145（红髓）共标记。在这些器官的几乎所有细胞类型中都发现了IGF-I和两种IGF受体，转基因小鼠和对照动物中的模式相似。组织形态计量学分析显示胸腺皮质大小显著增加，脾脏小梁大小增加。这表明IGF-II的过量产生在胸腺皮质中诱导局部效应（自分泌/旁分泌），但在胸腺髓质中未诱导。脾脏小梁生长很可能是IGF-II过量产生的远距离效应（旁分泌或内分泌）。
