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Differential expression of the bone and the liver tissue non-specific alkaline phosphatase isoforms in brain tissues


The enzyme tissue non-specific alkaline phosphatase (TNAP) belongs to the ectophosphatase family. It is present in large amounts in bone in which it plays a role in mineralization but little is known about its function in other tissues. Arguments are accumulating for its involvement in the brain, in particular in view of the neurological symptoms accompanying human TNAP deficiencies. We have previously shown, by histochemistry, alkaline phosphatase (AP) activity in monkey brain vessels and parenchyma in which AP exhibits specific patterns. Here, we clearly attribute this activity to TNAP expression rather than to other APs in primates (human and marmoset) and in rodents (rat and mouse). We have not found any brain-specific transcripts but our data demonstrate that neuronal and endothelial cells exclusively express the bone TNAP transcript in all species tested, except in mouse neurons in which liver TNAP transcripts have also been detected. Moreover, we highlight the developmental regulation of TNAP expression; this also acts during neuronal differentiation. Our study should help to characterize the regulation of the expression of this ectophosphatase in various cell types of the central nervous system.

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We thank Dr. Lászlo Négyessi (Semmelweiss University, Budapest, Hungary) and Gabor G. Kovacs (former National Institute of Psychiatry and Neurology, Budapest, Hungary) for support and advice and for providing human samples. We are grateful to Prof. Jean Sautet for his valuable expertise in embryonic anatomy. We thank Luc Renaud for the histology work. We acknowledge Prof. Odile Kellermann and Prof. Jean-Marie Launay for material derived from the 1C11 neuronal model. We are also grateful to Simon Heath for careful reading of the manuscript.

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Correspondence to Caroline Fonta.

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This study was supported by PHC Egide (Balaton 17341UE), CNRS (PICS 4331), Hypophosphatasie Europe, the University of Toulouse (ASUPS and ATUPS) and the French Embassy in Beijing.

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Fig. S1

Alignment of ALPL exon 1A including the 2-kb upstream sequence from five primate species; the 2142 bp including ALPL exon 1A (bold) and the 2050-bp upstream sequence from human were aligned with homologous sequences from chimpanzee, orangutan, macaque rhesus and marmoset. Note that 200-250 bp are missing from the orangutan sequence because of the incomplete sequencing in this species. Predicted or validated regulatory elements are highlighted: yellow vitamin-D-regulating elements (Matinspector prevision software, this study), green TATA box (Orimo and Shimada 2005), grey Sp1/Sp3-binding sites (Orimo and Shimada 2005; Yusa et al. 2000), turquoise sequence resembling retinoic-acid-responsive element (DR2 motif; Orimo and Shimada 2005). The arrow indicates the major transcription start site (position 2050 in the human sequence) (PDF 38 kb)

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Brun-Heath, I., Ermonval, M., Chabrol, E. et al. Differential expression of the bone and the liver tissue non-specific alkaline phosphatase isoforms in brain tissues. Cell Tissue Res 343, 521–536 (2011).

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  • Ectophosphatase
  • Cerebral endothelial cell
  • Neuron
  • Primate
  • Rodent