Coexpression of human cdk5 and its activator p35 with human protein tau in neurons in brain of triple transgenic mice.
The potential contribution of cyclin-dependent protein kinase 5 (cdk5) to hyperphosphorylate protein tau, as claimed in Alzheimer's disease, was investigated in vivo. We generated single, double, and triple transgenic mice that coexpress human cdk5 and its activator p35 as well as human protein tau in cerebral neurons. Whereas expression and increased cdk5-kinase activity was obtained, as measured in vitro and demonstrated in vivo, neither murine nor human protein tau was appreciably phosphorylated in the brain of double and triple transgenic mice. These mice behaved and reproduced normally. Silver impregnation and immunohistochemistry of brain sections demonstrated that neurofilament proteins became redistributed in apical dendrites of cortical neurons. This suggested a cytoskeletal effect, but no other relevant brain pathology became apparent. These observations indicate that cdk5/p35 is not a major protein tau kinase and that cdk5/p35 did not cause neurodegeneration in mouse brain, as opposed to cdk5/p25.
Van den Haute
C
C
Experimental Genetics Group, Center for Human Genetics, Flemish Institute for Biotechnology (VIB), Gasthuisberg O&N 06, Leuven, B-3000, Belgium.
Spittaels
K
K
Van Dorpe
J
J
Lasrado
R
R
Vandezande
K
K
Laenen
I
I
Geerts
H
H
Van Leuven
F
F
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001923:Brain Chemistry; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011233:Precipitin Tests; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D016622:Silver Staining; D016875:tau Proteins / Q000096:biosynthesis*
D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; C089495:neuronal Cdk5 activator (p25-p35); D016875:tau Proteins; D012313:RNA; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases