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Author(s): Ohshima T; Ward JM; Huh CG; Longenecker G; Veeranna; Pant HC; Brady RO; Martin LJ; Kulkarni AB
Title: Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death
Source: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 93 (20): 11173-11178
Date: 1996 OCT 1
Document Type: Journal : Article
DOI:
Language: English
Comment:
Address: NIDA,GENE TARGETING RES & CORE FACIL,NIH,BETHESDA,MD 20892.
NINCDS,DEV & METAB NEUROL BRANCH,NIH,BETHESDA,MD 20892. NINCDS,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. NCI,VET & TUMOR PATHOL SECT,OFF LAB ANIM SCI,NIH,FREDERICK,MD 21702. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,NEUROPATHOL LAB,BALTIMORE,MD 21205. Reprint:
E-mail:
Author Keywords:
KeyWords Plus: DIRECTED PROTEIN-KINASE; GANGLION-CELL NEURONS; NEUROFILAMENT PROTEINS;
POSTTRANSLATIONAL MODIFICATION; MAMMALIAN NEUROFILAMENTS;
PHOSPHORYLATION SITES; CDC2-LIKE KINASE; AXONAL-TRANSPORT; BRAIN; TAU
Abstract: Although cyclin-dependent kinase 5 (Cdk5) is closely related to other cyclin-dependent kinases, its kinase activity is detected only in the postmitotic neurons. Cdk5 expression and kinase activity are correlated with the extent of differentiation of neuronal cells in developing brain, Cdk5 purified from nervous tissue phosphorylates neuronal cytoskeletal proteins including neurofilament proteins and microtubule-associated protein tau in vitro. These findings indicate that Cdk5 may have unique functions in neuronal cells, especially in the regulation of phosphorylation of cytoskeletal molecules, We report here generation of Cdk5(-/-) mice through gene targeting and their phenotypic analysis. Cdk5(-/-) mice exhibit unique lesions in the central nervous system associated with perinatal mortality. The brains of Cdk5(-/-) mice lack cortical laminar structure and cerebellar foliation, In addition, the large neurons in the brain stem and in the spinal cord show chromatolytic changes with accumulation of neurofilament immunoreactivity. These findings indicate that Cdk5 is an important molecule for brain development and neuronal differentiation and also suggest that Cdk5 may play critical roles in neuronal cytoskeleton structure and organization.
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