Document Detail

Lack of PPCA expression only partially coincides with lysosomal storage in galactosialidosis mice: indirect evidence for spatial requirement of the catalytic rather than the protective function of PPCA.
MedLine Citation:
PMID:  9736781     Owner:  NLM     Status:  MEDLINE    
Protective protein/cathepsin A (PPCA) is a pleiotropic lysosomal enzyme that complexes with beta-galactosidase and neuraminidase, and possesses serine carboxypeptidase activity. Its deficiency in man results in the neurodegenerative lysosomal storage disorder galactosialidosis (GS). The mouse model of this disease resembles the human early onset phenotype and results in severe nephropathy and ataxia. To understand better the pathophysiology of the disease, we compared the occurrence of lysosomal PPCA mRNA and protein in normal adult mouse tissues with the incidence of lysosomal storage in PPCA(-/-) mice. PPCA expression was markedly variable among different tissues. Most sites that produced both mRNA and protein at high levels in normal mice showed extensive and overt storage in the knockout mice. However, this correlation was not consistent as some cells that normally expressed high levels of PPCA were unaffected in their storage capability in the PPCA(-/-) mice. In addition, some normally low expressing cells accumulated large amounts of undegraded products in the GS mouse. This apparent discrepancy may reflect a requirement for the catalytic rather than the protective function of PPCA and/or the presence of cell-specific substrates in certain cell types. A detailed map showing the cellular distribution of PPCA in nomal mouse tissues as well as the sites of lysosomal storage in deficient mice is critical for accurate assessment of the effects of therapeutic interventions.
R J Rottier; C N Hahn; L W Mann; M del Pilar Martin; R J Smeyne; K Suzuki; A d'Azzo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Human molecular genetics     Volume:  7     ISSN:  0964-6906     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1998-12-01     Completed Date:  1998-12-01     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1787-94     Citation Subset:  IM    
Department of Genetics and Department of Developmental Neurobiology, St Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA.
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MeSH Terms
Brain / enzymology,  pathology
Carboxypeptidases / genetics*,  metabolism*
Cathepsin A
Epididymis / enzymology,  pathology
In Situ Hybridization
Intestines / enzymology,  pathology
Liver / enzymology,  pathology
Lysosomal Storage Diseases / genetics*,  pathology*
Mice, Inbred Strains
Mice, Knockout
Ovary / enzymology,  pathology
Spleen / enzymology,  pathology
Testis / enzymology,  pathology
Uterus / enzymology,  pathology
Grant Support
Reg. No./Substance:
EC 3.4.-/Carboxypeptidases; EC A

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