Document Detail

Biochemical and behavioural phenotyping of a mouse model for GAMT deficiency.
MedLine Citation:
PMID:  15792821     Owner:  NLM     Status:  MEDLINE    
Deficiency of guanidinoacetate N-methyltransferase (GAMT) is the first described creatine (CT) deficiency syndrome in man, biochemically characterized by accumulation of guanidinoacetic acid (GAA) and depletion of CT. Patients exhibit severe developmental and muscular problems. We created a mouse model for GAMT deficiency, which exerts biochemical changes comparable with those found in human GAMT-deficient subjects. CT and creatinine (CTN) levels are significantly decreased and GAA is increased in knockout (KO) mice. In patients, other guanidino compounds (GCs) appear to be altered as well, which may also contribute to the symptomatology. Extensive evaluation of GCs levels in the GAMT mouse model was therefore considered appropriate. Concentrations of 13 GCs in plasma, 24-h urine, brain and muscle of GAMT mice were measured. We also report on the detailed behavioural characterization of this model for GAMT deficiency. Besides an increase of GAA and a decrease of CT and CTN in plasma, 24-h urine, brain and muscle of KO mice, we observed a significant increase of other GCs in brain and muscle that was sometimes reflected in plasma and/or urine. KO mice displayed mild cognitive impairment. In general, it could be concluded that the GAMT mouse model is very useful for biochemical research of GAMT deficiency, but shows only a mild cognitive deficit.
An Torremans; Bart Marescau; Ilse Possemiers; Debby Van Dam; Rudi D'Hooge; Dirk Isbrandt; Peter Paul De Deyn
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the neurological sciences     Volume:  231     ISSN:  0022-510X     ISO Abbreviation:  J. Neurol. Sci.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-03-28     Completed Date:  2005-06-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375403     Medline TA:  J Neurol Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  49-55     Citation Subset:  IM    
Laboratory of Neurochemistry and Behaviour/Born Bunge Foundation, University of Antwerp, Department of Biomedical Sciences, Universiteitsplein 1, 2610 Antwerp (Wilrijk), Belgium.
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MeSH Terms
Behavior, Animal / physiology*
Brain Chemistry*
Creatine / deficiency,  metabolism
Creatinine / metabolism
Deficiency Diseases / genetics,  metabolism*,  physiopathology*
Disease Models, Animal
Exploratory Behavior / physiology
Glycine / analogs & derivatives*,  metabolism
Guanidinoacetate N-Methyltransferase
Memory / physiology
Methyltransferases / deficiency*,  genetics
Mice, Inbred C57BL
Mice, Knockout
Motor Activity / genetics
Muscles / metabolism
Neuropsychological Tests
Psychomotor Performance / physiology
Reaction Time / genetics
Rotarod Performance Test / methods
Spatial Behavior / physiology
Reg. No./Substance:
352-97-6/glycocyamine; 56-40-6/Glycine; 57-00-1/Creatine; 60-27-5/Creatinine; EC 2.1.1.-/Methyltransferases; EC N-Methyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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