title: Impact of beta-galactosidase mutations on the expression of the canine lysosomal multienzyme complex.
abstract: beta-galactosidase (GLB1) forms a functional lysosomal multienzyme complex with lysosomal protective protein (PPCA) and neuraminidase 1 (NEU1) which is important for its intracellular processing and activity. Mutations in the beta-galactosidase gene cause the lysosomal storage disease G(M1)-gangliosidosis. In order to identify additional molecular changes associated with the presence of beta-galactosidase mutations, the expression of canine lysosomal multienzyme complex components in GLB1(+/+), GLB1(+/-) and GLB1(-/-) fibroblasts was investigated by quantitative RT-PCR, Western blot and enzymatic assays. Quantitative RT-PCR revealed differential regulation of total beta-galactosidase, beta-galactosidase variants and protective protein for beta-galactosidase gene (PPGB) in GLB1(+/-) and GLB1(-/-) compared to GLB1(+/+) fibroblasts. Furthermore, it was shown that PPGB levels gradually increased with the number of mutant beta-galactosidase alleles while no change in the NEU1 expression was observed. This is the first study that simultaneously examine the effect of GLB1(+/+), GLB1(+/-) and GLB1(-/-) genotypes on the expression of lysosomal multienzyme complex components. The findings reveal a possible adaptive process in GLB1 homozygous mutant and heterozygous individuals that could facilitate the design of efficient therapeutic strategies.
authors.affiliation: Department of Pathology, University of Veterinary Medicine, Hannover, Bünteweg 17, D-30559, Hannover, Germany. robert.kreutzer@tiho-hannover.de
authors.forename: Robert
authors.initials: R
authors.lastname: Kreutzer
authors.forename: Mihaela
authors.initials: M
authors.lastname: Kreutzer
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Sewell
authors.forename: Somporn
authors.initials: S
authors.lastname: Techangamsuwan
authors.forename: Tosso
authors.initials: T
authors.lastname: Leeb
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumgärtner
mesh_terms: D000818:Animals; D043402:Cathepsin A / Q000235:genetics* / Q000378:metabolism; D004285:Dogs; D005347:Fibroblasts / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D008247:Lysosomes / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009439:Neuraminidase / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D001616:beta-Galactosidase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D009097:Multienzyme Complexes; D012333:RNA, Messenger; D009439:Neuraminidase; D001616:beta-Galactosidase; D043402:Cathepsin A