Prerequisites for tissue specific and position independent expression of a gene locus in transgenic mice

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
C BoniferA E Sippel

Abstract

The elucidation of general parameters influencing the transcriptional activation of gene loci at distinct stages of development is an essential prerequisite for a reproducibly successful gene transfer in both gene therapy protocols and biotechnology. Up to now research has focused mostly on the identification and characterization of individual cis-regulatory elements by transient transfection and in vitro assays. However, the most relevant assay system to test gene constructs designed for gene therapy protocols is the transgenic animal. In such an experimental system exogenous genes are usually integrated randomly in the chromatin. For gene constructs not fulfilling the requirements for correct gene locus activation this can lead to genomic position effects on gene expression. The consequences are highly variable expression levels and a disturbance of temporal and spatial expression patterns. Hence it is important to examine how cis-elements function in a chromatin context, and how they cooperate during the developmentally controlled activation of an entire gene locus. One among a few gene loci which are sufficiently characterized to enable such investigations is the chicken lysozyme locus. This review summarizes recent results...Continue Reading

Citations

Feb 24, 2000·Nucleic Acids Research·H WallaceJ McWhir
Feb 22, 2001·Journal of Molecular and Cellular Cardiology·A A DempseyC C Liew
Apr 6, 2005·BMC Immunology·Nives ZimmermannMarc E Rothenberg

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