Cells from transgenic mice expressing a human mini-gene for collagen I were used as markers to follow the fate of mesenchymal precursor cells from marrow that were partially enriched by adherence to plastic, expanded in culture, and then injected into irradiated mice. Sensitive PCR assays for the marker collagen I gene indicated that few of the donor cells were present in the recipient mice after 1 week, but 1-5 months later, the donor cells accounted for 1.5-12% of the cells in bone, cartilage, and lung in addition to marrow and spleen. A PCR in situ assay on lung indicated that the donor cells diffusely populated the parenchyma, and reverse transcription-PCR assays indicated that the marker collagen I gene was expressed in a tissue-specific manner. The results, therefore, demonstrated that mesenchymal precursor cells from marrow that are expanded in culture can serve as long-lasting precursors for mesenchymal cells in bone, cartilage, and lung. They suggest that cells may be particularly attractive targets for gene therapy ex vivo.

No abstract

To examine molecular mechanisms associated with schizophrenia this study measured expression of approximately 12,000 genes in the middle temporal gyrus from 12 subjects with schizophrenia and 14 matched normal controls. Among the most consistent changes in genes with robust expression were significant decreases in the expression of myelination-related genes MAG, PLLP (TM4SF11), PLP1, ERBB3 in subjects with schizophrenia. There was also altered expression of genes regulating neurodevelopment (TRAF4, Neurod1, histone deacetylase 3), a circadian pacemaker (PER1), and several other genes involved in regulation of chromatin function and signaling mechanisms. These findings support the hypothesis that schizophrenia is associated with abnormalities in oligodendroglia and provide initial evidence suggesting a role for epigenetic mechanisms and altered circadian rhythms in this disorder.

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A genetic association between schizophrenia and a silent C/T(102) polymorphism in the 5-HT2A receptor gene (5-HT2AR) has been previously reported; however, the mechanisms underlying this association remain unknown. Here we developed an improved quantitative assay for measurements of allele ratios, which revealed that the expression of allele "C" in the temporal cortex of normal heterozygous individuals was significantly lower than the expression of allele "T" (allele "C" to allele "T" ratio of approximately 0.8, P < 0.0001). Confirming decreased expression of allele "C," total levels of 5-HT2AR mRNA and protein in normal individuals with the C/C genotype were lower than in individuals with the T/T genotype. Similarly to normal individuals, allele "C" to allele "T" ratio in heterozygous schizophrenics was reduced (approximately 0.8, P < 0001). This ratio was independent of neuroleptic treatment history. By contrast, total levels of 5-HT2AR mRNA correlated inversely with neuroleptic free interval prior to death (r = -0.67, P < 0.001) suggesting a reversible neuroleptic effect. Total levels 5-HT2AR mRNA in neuroleptic free (> 26 weeks) schizophrenics (n = 11) were significantly lower than in controls (P = 0.03). The data suggest that increased prevalence of allele "C" among schizophrenics may be due to intrinsically low expression of this allele, which may contribute to a deficit in 5-HT2AR expression in some schizophrenics.