Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells.

Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells. Abstract Text:

X Y Zhou,H Morreau,R Rottier,D Davis,E Bonten,N Gillemans,D Wenger,F G Grosveld,P Doherty,K Suzuki,G C Grosveld,A d'Azzo,

The lysosomal storage disorder galactosialidosis results from a primary deficiency of the protective protein/cathepsin A (PPCA), which in turn affects the activities of beta-galactosidase and neuraminidase. Mice homozygous for a null mutation at the PPCA locus present with signs of the disease shortly after birth and develop a phenotype closely resembling human patients with galactosialidosis. Most of their tissues show characteristic vacuolation of specific cells, attributable to lysosomal storage. Excessive excretion of sialyloligosaccharides in urine is diagnostic of the disease. Affected mice progressively deteriorate as a consequence of severe organ dysfunction, especially of the kidney. The deficient phenotype can be corrected by transplanting null mutants with bone marrow from a transgenic line overexpressing human PPCA in erythroid precursor cells. The transgenic bone marrow gives a more efficient and complete correction of the visceral organs than normal bone marrow. Our data demonstrate the usefulness of this animal model, very similar to the human disease, for experimenting therapeutic strategies aimed to deliver the functional protein or gene to affected organs. Furthermore, they suggest the feasibility of gene therapy for galactosialidosis and other disorders, using bone marrow cells engineered to overexpress and secrete the correcting lysosomal protein.

Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells. Publishing Authors By Initials

XY Zhou,H Morreau,R Rottier,D Davis,E Bonten,N Gillemans,D Wenger,FG Grosveld,P Doherty,K Suzuki,GC Grosveld,A d'Azzo,

For similar enzymes and coenzymes: enzymes: hydrolases: glycoside hydrolases: galactosidases: beta-galactosidase research abstracts see: enzymes and coenzymes: enzymes: hydrolases: glycoside hydrolases: galactosidases: beta-galactosidase research

PUBMED ID PMID:

MEDLINE DATE:

Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Genes & development

VOLUME: 9

Page Numbers: 2623-34

Journal Abbreviation:

ISSN: 0890-9369

DAY: 1

MONTH: Nov

YEAR: 1995

Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8711660

Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells. Keywords Mesh Terms:

KEYWORDS: beta-Galactosidase

MESH TERMS: deficiency

Chemical & Substance for Abstract: Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells. Information

Substance Name: PPGB protein, human

Registry Number: EC 3.4.16.5

Grant and Affiliation Information for Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells.

AFFILIATION: Department of Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

Country: UNITED STATES

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Genes Dev

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells Related Publications

• Correction of murine galactosialidosis by bone marrow-derived macrophages overexpressing human protective protein/cathepsin A under control of the colony-stimulating factor-1 receptor promoter.
• Early-infantile galactosialidosis: clinical, biochemical, and molecular observations in a new patient.
• Expression of cDNA encoding the human "protective protein" associated with lysosomal beta-galactosidase and neuraminidase: homology to yeast proteases.
• Identification of the promoters for the human and murine protective protein/cathepsin A genes.
• Molecular and biochemical analysis of protective protein/cathepsin A mutations: correlation with clinical severity in galactosialidosis.
• Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells.
• Neuraminidase 1 is a negative regulator of lysosomal exocytosis.
• Systemic and neurologic abnormalities distinguish the lysosomal disorders sialidosis and galactosialidosis in mice.
• The atomic model of the human protective protein/cathepsin A suggests a structural basis for galactosialidosis.
• Transport of human lysosomal neuraminidase to mature lysosomes requires protective protein/cathepsin A.