Unchanged scrapie pathology in brain tissue of tyrosine kinase Fyn-deficient mice.
Fyn is a 59-kDa member of the Src family of tyrosine kinases synthesized on cytosolic polysomes and then targeted to the plasma membrane where it clusters in caveolae-like membrane microdomains. The cellular isoform of the prion protein (PrP) has also been identified to be a caveolar constituent and to participate in signal transduction events concerning cell survival and differentiation via recruitment of Fyn. We studied the scrapie infection of mice deficient for Fyn (Fyn(-/-)) to clarify the role of Fyn in an in vivo model of transmissible spongiforme encephalopathies. Fyn(-/-) mice died on average 9 days earlier than wild-type control mice, but no differences were seen regarding activation of astrocytes, vacuolization of the neuropil, and accumulation of misfolded prion protein. The experimental model suggests that a deficiency for Fyn is detrimental in prion diseases, although it has no major effect on the clinical course of an experimental prion infection of the CNS.
Schwarz
Anja
A
Project Neurodegenerative Diseases, Robert Koch Institute, Berlin, Germany.
Burwinkel
Michael
M
Riemer
Constanze
C
Schultz
Julia
J
Baier
Michael
M
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019581:Neuropil / Q000201:enzymology / Q000473:pathology; D018620:PrPSc Proteins / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics*; D012608:Scrapie / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D018620:PrPSc Proteins; D051076:Proto-Oncogene Proteins c-fyn