Biomedical subjects

Marko Piirsoo

Publications and source records attributed to Marko Piirsoo.

4 recordsLinked to original sources

PubMed2007

Mouse and rat BDNF gene structure and expression revisited.

Brain-derived neurotrophic factor (BDNF) has important functions in the development of the nervous system and in brain plasticity-related processes such as memory, learning, and drug addiction. Despite the fact that the function and regulation of rodent BDNF gene expression have received close attention during the last decade, knowledge of the structural organization of mouse and rat BDNF gene has remained incomplete. We have identified and characterized several mouse and rat BDNF transcripts containing novel 5' untranslated exons and introduced a new numbering system for mouse and rat BDNF exons. According to our results both mouse and rat BDNF gene consist of eight 5' untranslated exons and one protein coding 3' exon. Transcription of the gene results in BDNF transcripts containing one of the eight 5' exons spliced to the protein coding exon and in a transcript containing only 5' extended protein coding exon. We also report the distinct tissue-specific expression profiles of each of the mouse and rat 5' exon-specific transcripts in different brain regions and nonneural tissues. In addition, we show that kainic acid-induced seizures that lead to changes in cellular Ca(2+) levels as well as inhibition of DNA methylation and histone deacetylation contribute to the differential regulation of the expression of BDNF transcripts. Finally, we confirm that mouse and rat BDNF gene loci do not encode antisense mRNA transcripts, suggesting that mechanisms of regulation for rodent and human BDNF genes differ substantially.

Animals↗

PubMed2003

The POU proteins Brn-2 and Oct-6 share important functions in Schwann cell development.

The genetic hierarchy that controls myelination of peripheral nerves by Schwann cells includes the POU domain Oct-6/Scip/Tst-1and the zinc-finger Krox-20/Egr2 transcription factors. These pivotal transcription factors act to control the onset of myelination during development and tissue regeneration in adults following damage. In this report we demonstrate the involvement of a third transcription factor, the POU domain factor Brn-2. We show that Schwann cells express Brn-2 in a developmental profile similar to that of Oct-6 and that Brn-2 gene activation does not depend on Oct-6. Overexpression of Brn-2 in Oct-6-deficient Schwann cells, under control of the Oct-6 Schwann cell enhancer (SCE), results in partial rescue of the developmental delay phenotype, whereas compound disruption of both Brn-2 and Oct-6 results in a much more severe phenotype. Together these data strongly indicate that Brn-2 function largely overlaps with that of Oct-6 in driving the transition from promyelinating to myelinating Schwann cells.

Animals↗

PubMed2003

Effective generation of transgenic mice by Bovine papillomavirus type 1 based self-replicating plasmid that is maintained as extrachromosomal genetic element in three generations of animals.

The objective of our study was to analyze the efficiency and the properties of the inheritance of the Bovine papillomavirus type 1 (BPV1) replicator-based plasmid used as vector system for generation of transgenic animals. Previously, we have characterized a series of self-replicating plasmid vectors containing all viral factors necessary and sufficient for stable extrachromosomal replication of the BPV1 genome in the tissue culture system. We also demonstrated that the designed replicating vector system has a considerable benefit in the transgene expression, if compared to the regular expression vector. The vector, which showed the highest stability and maintenance function in the tissue culture was chosen for generation of the transgenic mice by pronuclear injections of the circular supercoiled plasmid. This method resulted in successful production of transgenic animals. Transmission efficiency of the vectors into the F(1) generation of animals varied between 0 and 48%, whereas transmission into the F(2) generation was uniformly near 50%. The maintenance of the vector-plasmids in the F(2) generation of transgenic animals as extrachromosomal genetic element was demonstrated by rescue of the plasmid into the Escherichia coli.

Animals↗

PubMed2002

A cell type-specific allele of the POU gene Oct-6 reveals Schwann cell autonomous function in nerve development and regeneration.

While an important role for the POU domain transcription factor Oct-6 in the developing peripheral nerve has been well established, studies into its exact role in nerve development and regeneration have been hampered by the high mortality rate of newborn Oct-6 mutant animals. In this study we have generated a Schwann cell-specific Oct-6 allele through deletion of the Schwann cell-specific enhancer element (SCE) in the Oct-6 locus. Analysis of mice homozygous for this allele (deltaSCE allele) reveals that rate-limiting levels of Oct-6 in Schwann cells are dependent on the SCE and that this element does not contribute to Oct-6 regulation in other cell types. We demonstrate a Schwann cell autonomous function for Oct-6 during nerve development as well as in regenerating nerve. Additionally, we show that Krox-20, an important regulatory target of Oct-6 in Schwann cells, is activated, with delayed kinetics, through an Oct-6-independent mechanism in these mice.

Alleles↗