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.
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.
Li
A
A
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Medical Sciences, Nagasaki, Japan.
Sakaguchi
S
S
Shigematsu
K
K
Atarashi
R
R
Roy
B C
BC
Nakaoke
R
R
Arima
K
K
Okimura
N
N
Kopacek
J
J
Katamine
S
S
D000251:Adenosine Triphosphatases; D000818:Animals; D001259:Ataxia / Q000209:etiology / Q000235:genetics*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005656:Fungal Proteins; D058851:GPI-Linked Proteins; D015870:Gene Expression; D051379:Mice; D008817:Mice, Mutant Strains; D009410:Nerve Degeneration / Q000150:complications; D009474:Neurons / Q000502:physiology; D011328:Prions / Q000235:genetics* / Q000378:metabolism*; D011689:Purkinje Cells / Q000502:physiology; D020365:RNA Helicases; D000072260:RNA Splicing Factors; D029701:Saccharomyces cerevisiae Proteins
D005656:Fungal Proteins; D058851:GPI-Linked Proteins; D011328:Prions; C122036:Prnd protein, mouse; D000072260:RNA Splicing Factors; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; C075669:PRP16 protein, S cerevisiae; D020365:RNA Helicases