Expression profiling of sciatic nerve in a Charcot-Marie-Tooth disease type 1a mouse model.

Expression profiling was performed on sciatic nerve of normal mice and of transgenic mice overexpressing the peripheral myelin protein 22 kDa (PMP22). These mice represent a model for the hereditary peripheral neuropathy Charcot-Marie Tooth type 1A. Comparison of the profiles reveals that the proteasomal degradation pathway and various signaling mechanisms are up-regulated in the diseased nerve.

Ribonuclease H1 maps to chromosome 2 and has at least three pseudogene loci in the human genome.

We have analyzed the genomic structure of ribonuclease H1 (RNase H1) loci in the human genome. Human PAC library screening combined with database searches indicated that several loci are present. The transcribed gene is localized on chromosome 2p25.

Tumor genotype-specific growth inhibition in vivo by antisense oligonucleotides against a polymorphic site of the large subunit of human RNA polymerase II.

Loss of heterozygosity (LOH) reduces genes to hemizygosity in cancer cells and presents an absolute difference between normal and cancer cells. The regions of LOH are usually much larger than the tumor suppressor gene, which is lost, and are expected to contain genes that are essential for cell survival. Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation in man, often giving rise to two or more allelic forms of most genes.

The involvement of human ribonucleases H1 and H2 in the variation of response of cells to antisense phosphorothioate oligonucleotides.

We have analyzed the response of a number of human cell lines to treatment with antisense oligodeoxynucleotides (ODNs) directed against RNA polymerase II, replication protein A, and Ha-ras. ODN-delivery to the cells was liposome-mediated or via electroporation, which resulted in different intracellular locations of the ODNs. The ODN-mediated target mRNA reduction varied considerably between the cell lines.