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(American Journal of Pathology. 2000;157:1447-1452.)
© 2000 American Society for Investigative Pathology

Short Communications

Physiological Expression of the Gene for PrP-Like Protein, PrPLP/Dpl, by Brain Endothelial Cells and its Ectopic Expression in Neurons of PrP-Deficient Mice Ataxic Due to Purkinje Cell Degeneration

Aimin Li^*, Suehiro Sakaguchi^*, Kazuto Shigematsu, Ryuichiro Atarashi, Bhabesh C. Roy, Ryota Nakaoke, Kazuhiko Arima, Nobuhiko Okimura^*, Juraj Kopacek^§ and Shigeru Katamine^*

From the Department of Molecular Microbiology and Immunology,^*
Nagasaki University Graduate School of Medical Sciences, Nagasaki, Japan; the Departments of Bacteriology
and Pathology II,
Nagasaki University School of Medicine, Nagasaki, Japan; and the Department of Molecular Biology,^§
Institute of Virology, Slovak Academy of Sciences, Brastislava, Slovakia

Recently, a novel gene encoding a prion protein (PrP)-like glycoprotein, PrPLP/Dpl, was identified as being expressed ectopically by neurons of the ataxic PrP-deficient (Prnp^-/-) mouse lines exhibiting Purkinje cell degeneration. In adult wild-type mice, PrPLP/Dpl mRNA was physiologically expressed at a high level by testis and heart, but was barely detectable in brain. However, transient expression of PrPLP/Dpl mRNA was detectable by Northern blotting in the brain of neonatal wild-type mice, showing maximal expression around 1 week after birth. In situ hybridization paired with immunohistochemistry using anti-factor VIII serum identified brain endothelial cells as expressing the transcripts. Moreover, in the neonatal wild-type mice, the PrPLP/Dpl mRNA colocalized with factor VIII immunoreactivities in spleen and was detectable on capillaries in lamina propria mucosa of gut. These findings suggested a role of PrPLP/Dpl in angiogenesis, in particular blood-brain barrier maturation in the central nervous system. Even in the ataxic Ngsk Prnp^-/- mice, the physiological regulation of PrPLP/Dpl mRNA expression in brain endothelial cells was still preserved. This strongly supports the argument that the ectopic expression of PrPLP/Dpl in neurons, but not deregulation of its physiological expression in endothelial cells, is involved in the neuronal degeneration in ataxic Prnp^-/- mice.

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