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The Journal of Neuroscience, January 15, 2001, 21(2):550-558
Neuronal Cyclin-Dependent Kinase 5 Activity Is Critical for
Survival
Teruyuki
Tanaka1, 2,
Veeranna3,
Toshio
Ohshima1, 2,
Prithi
Rajan4,
Niranjana D.
Amin3,
Andrew
Cho1,
Taduru
Sreenath1,
Harish C.
Pant3,
Roscoe O.
Brady2, and
Ashok B.
Kulkarni1
1 Functional Genomics Unit, Gene Targeting Facility,
National Institute of Dental and Craniofacial Research, and
2 Developmental and Metabolic Neurology Branch,
3 Laboratory of Neurochemistry, and
4 Laboratory of Molecular Biology, National Institute of
Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, Maryland 20892
Cyclin-dependent kinase 5 (Cdk5) null mice exhibit a unique
phenotype characterized by perinatal mortality, disrupted cerebral cortical layering attributable to abnormal neuronal migration, lack of cerebellar foliation, and chromatolytic changes of neurons in
the brainstem and the spinal cord. Because Cdk5 is expressed in both
neurons and astrocytes, it has been unclear whether this phenotype is
primarily attributable to defects in neurons or in astrocytes. Herein
we report reconstitution of Cdk5 expression in neurons in Cdk5 null
mice and its effect on the null phenotype. Unlike the Cdk5 null mice,
the reconstituted Cdk5 null mice that express the Cdk5 transgene under
the p35 promoter (TgKO mice) were viable and fertile. Because Cdk5
expression is mainly limited to neurons in these mice and rescues the
defects in the nervous system of the Cdk5 null phenotype, it clearly
demonstrates that Cdk5 activity is necessary for normal development and
survival of p35-expressing neurons.
Key words:
Cdk5; cerebrum; cerebellum; neuron; astrocyte; phosphorylation; neurodegeneration; transgenic mice
Copyright © 2001 Society for Neuroscience 0270-6474/01/212550-09$05.00/0
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