Teratomas are benign tumors that form after ectopic injection of embryonic stem (ES) cells into mice and contain derivatives of all primitive germ layers. To study the role of β1 integrin during teratoma formation, we compared teratomas induced by normal and β1-null ES cells. Injection of normal ES cells gave rise to large teratomas. In contrast, β1-null ES cells either did not grow or formed small teratomas with an average weight of <5% of that of normal teratomas. Histological analysis of β1-null teratomas revealed the presence of various differentiated cells, however, a much lower number of host-derived stromal cells than in normal teratomas. Fibronectin, collagen I, and nidogen were expressed but, in contrast to normal teratomas, diffusely deposited in β1-null teratomas. Basement membranes were present but with irregular shape and detached from the cell surface.Normal teratomas had large blood vessels with a smooth inner surface, containing both host- and ES cell–derived endothelial cells. In contrast, β1-null teratomas had small vessels that were loosely embedded into the connective tissue. Furthermore, endothelial cells were always of host-derived origin and formed blood vessels with an irregular inner surface. Although β1- deficient endothelial cells were absent in teratomas, β1-null ES cells could differentiate in vitro into endothelial cells. The formation of a complex vasculature, however, was significantly delayed and of poor quality in β1-null embryoid bodies. Moreover, while vascular endothelial growth factor induced proliferation of endothelial cells as well as an extensive branching of blood vessels in normal embryoid bodies, it had no effect in β1-null embryoid bodies.
Transgenic technology has developed at breakneck speed in the past years. The establishment of embryonic stem cells and the finding that they can serve as bridge between genetic manipulations in vitro and biological analysis in vivo enabled the systematic creation of mouse strains with defined genetic alterations. This review lists the strategies which can be used to alter the genetic makeup of mice and summarizes some of the results which have been obtained in genetically altered mice of immunological interest.
Kreide Versteinerungen sind bisjetzt nur im mittleren Java, in der Residenz Banjumas, gefunden, zwischen Watu belah und Sirongge. Sie gehören zu Orbitolina concava (S. V, 27; V. F., 1091) und befinden sich in einem krystallinischen Kalke, welcher in Serpentin eingelagert ist. Da die genann¬ ten Foraminiferen zum Aufbau ihrer Schalen Quarzkörner verwenden, so müssen präexistierende, quarzreiche Gesteine ihnen dafür das Material geliefert haben, und es liegt nahe, in diesem Verbände an die granatführenden Glimmerschiefer desselben Gebietes zu denken,' über deren Alter die An¬ sichten sehr gewechselt haben (S. VI, 244), für die aber Niethammer gewiss mit Recht ein palaeozoisches oder noch höheres Alter annimmt (1909, 267). Die Orbitolinen zeigen zudem an, das die Küste der Kreidezeit in der Nähe ihres jetzigen Fundortes verlief. Sie lassen sich nicht von den auf Borneo vorkommenden Orbitolinen unterscheiden, welche im Stromgebiete des Kapuas, am Seberuang und am Bojan, gefunden sind und für die ich ein cenomanes Alter als wahrscheinlich annahm (S. IV, 211).
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