PMID- 9825944
OWN - NLM
STAT- MEDLINE
DCOM- 19981211
LR  - 20211203
IS  - 0022-3069 (Print)
IS  - 0022-3069 (Linking)
VI  - 57
IP  - 11
DP  - 1998 Nov
TI  - Alterations in cyclin-dependent protein kinase 5 (CDK5) protein levels, activity 
      and immunocytochemistry in canine motor neuron disease.
PG  - 1070-7
AB  - Hereditary canine spinal muscular atrophy (HCSMA) is a dominantly inherited motor 
      neuron disease in Brittany spaniels that is clinically characterized by 
      progressive muscle weakness leading to paralysis. Histopathologically, 
      degeneration is confined to motor neurons with accumulation of phosphorylated 
      neurofilaments in axonal internodes. Cyclin-dependent kinase 5 (CDK5), a kinase 
      related to the cell cycle kinase cdc2, phosphorylates neurofilaments and 
      regulates neurofilament dynamics. We examined CDK5 activity, protein levels, and 
      cellular immunoreactivity in nervous tissue from dogs with HCSMA, from closely 
      age-matched controls and from dogs with other neurological diseases. On 
      immunoblot analysis, CDK5 protein levels were increased in the HCSMA dogs (by 
      approximately 1.5-fold in both the cytosolic and the particulate fractions). CDK5 
      activity was significantly increased (by approximately 3-fold) in the particulate 
      fractions in the HCSMA dogs compared to all controls. The finding that CDK5 
      activity was increased in the young HCSMA homozygotes with the accelerated form 
      of the disease, who do not show axonal swellings histologically, suggests that 
      alterations in CDK5 occurs early in the pathogenesis, prior to the development of 
      significant neurofilament pathology. Immunocytochemically, there was strong CDK5 
      staining of the nuclei, cytoplasm and axonal processes of the motor neurons in 
      both control dogs and dogs with HCSMA. Further immunocytochemical studies 
      demonstrated CDK5 staining where neurofilaments accumulated, in axonal swellings 
      in the dogs with HCSMA. Our observations suggest phosphorylation-dependent events 
      mediated by CDK5 occur in canine motor neuron disease.
FAU - Green, S L
AU  - Green SL
AD  - Department of Comparative Medicine, Stanford University School of Medicine, CA 
      94305-5410, USA.
FAU - Vulliet, P R
AU  - Vulliet PR
FAU - Pinter, M J
AU  - Pinter MJ
FAU - Cork, L C
AU  - Cork LC
LA  - eng
GR  - NS 31621/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Animals
MH  - Axons/enzymology
MH  - Brain/enzymology
MH  - Cyclin-Dependent Kinase 5
MH  - *Cyclin-Dependent Kinases
MH  - Dog Diseases/*enzymology/*genetics/pathology
MH  - Dogs
MH  - Female
MH  - Immunoblotting
MH  - Immunohistochemistry
MH  - Male
MH  - Muscular Atrophy, Spinal/*enzymology/genetics/pathology/*veterinary
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Reference Values
MH  - Spinal Cord/enzymology/pathology
MH  - Tissue Distribution
EDAT- 1998/11/24 00:00
MHDA- 1998/11/24 00:01
CRDT- 1998/11/24 00:00
PHST- 1998/11/24 00:00 [pubmed]
PHST- 1998/11/24 00:01 [medline]
PHST- 1998/11/24 00:00 [entrez]
AID - 10.1097/00005072-199811000-00010 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 1998 Nov;57(11):1070-7. doi: 
      10.1097/00005072-199811000-00010.