CHARACTERIZATION OF TRANSGENIC MICE WITH AN INCREASED CONTENT OF CHROMOSOMAL PROTEIN HMG-14 IN THEIR CHROMATIN

Chromosomal protein HMG-14 is a ubiquitous nuclear protein that may mo dulate the chromatin structure of transcriptionally active genes, To g ain insights into the cellular function of the HMG-14 protein, we gene rated two transgenic mouse lines carrying either two or six copies of the human HMG-14 gene, The transgenic mice express human HMG-14 mRNA a nd protein in all tissues examined at a level reflecting the increased gene dosage, suggesting that the HMG14 transgene contains all the con trol regions necessary for regulated gene expression, Expression of th e human HMG-14 protein does not alter the expression of the endogenous mouse HMG-14 protein or its close homolog, protein HMG-17. The intrac ellular distribution of the exogenous human protein is indistinguishab le from that of the endogenous mouse protein, resulting in a three-fol d increase in the level of the chromatin-bound HMG-14, The transgenic mice had a higher incidence of epithelial cysts in their thymus than d id control animals, We conclude that the cellular levels of HMG-14/-17 are determined by gene copy number, that the DNA fragment containing the gene and about 1,000 bp flanking its 5' and 3' ends contain most o f the elements necessary for gene expression, that the upper limits of HMG-14 in chromatin are not stringently regulated, and that a three-f old increase in chromatin-bound protein cause only mild phenotypic cha nges in the transgenic mice.