Reduced Mcm2 expression results in severe stem/progenitor cell deficiency and cancer.

Mcm2 is a component of the DNA replication licensing complex that marks DNA replication origins during G1 of the cell cycle for use in the subsequent S-phase. It is expressed in stem/progenitor cells in a variety of regenerative tissues in mammals. Here, we have used the Mcm2 gene to develop a transgenic mouse in which somatic stem/progenitor cells can be genetically modified in the adult.

Stem/progenitor cell-specific enhanced green fluorescent protein expression driven by the endogenous Mcm2 promoter.

Previous studies have demonstrated expression of the minichromosome maintenance protein Mcm2 in cells that remain competent to divide, including stem/progenitor cells of the subventricular zone (SVZ) within the brain. Here, a transgenic mouse line in which the Mcm2 gene drives expression of enhanced green fluorescent protein (EGFP) was constructed by insertion of an internal ribosomal entry site (IRES)-EGFP cassette into the last exon of the gene, 3' to the stop codon. In these mice, expression of EGFP is observed in the SVZ and several other tissues with high proliferative activity, including the spleen, intestine, hair follicles, and bone marrow.

Accumulation of mutations and somatic selection in aging neural stem/progenitor cells.

Genomic instability within somatic stem cells may lead to the accumulation of mutations and contribute to cancer or other age-related phenotypes. However, determining the frequency of mutations that differ among individual stem cells is difficult from whole tissue samples because each event is diluted in the total population of both stem cells and differentiated tissue. Here the ability to expand neural stem/progenitor cells clonally permitted measurement of genomic alterations derived from a single initial cell.