Disease relevance of Glb1

• Generalized CNS disease and massive GM1-ganglioside accumulation in mice defective in lysosomal acid beta-galactosidase [1].
• II3NeuAc-GgOse4Cer (GM1) gangliosidosis is an incurable lysosomal storage disease caused by a deficiency in acid beta-galactosidase (beta-gal), resulting in the accumulation of ganglioside GM1 and its asialo derivative GgOse4Cer (GA1) in the central nervous system, primarily in the brain [2].
• Both the linear cloned viral DNA and a hybrid composed of mutant Bam HI (0.58) to Bgl I (0.72) 750 bp fragment (containing the origin of replication) ligated to the complementary wild-type 4.5 kb fragment are able to multiply on PCC4 embryonal carcinoma cells [3].
• The major surface polypeptide of the calf scours rotavirus is glycosylated, and highly purified beta-galactosidase (lactase) interacts with the virus in vitro causing removal of the outer shell of the capsid (uncoating) [4].
• Is lactase the receptor and uncoating enzyme for infantile enteritis (rota) viruses [4]?

High impact information on Glb1

• Our results indicate that Bgl-s acts cis, controlling the expression of the structural gene located on the same chromosome [5].
• The observed recombination frequency for the intervals between Fv-2 and Bgl-s was 6.8% [6].
• At least 10 centimorgans of Fv-2r-linked chromosomal material originating from the C57BL/6 ancestor remains in the D2.B6-Fv-2r genome, as shown by the continued presence of C57BL/6 alleles at the flanking Kfo-1 and Bgl-s loci [6].
• This hypothesis is consistent with the observations that rotaviruses seem to infect only gut epithelial cells, and that infant animals, whose lactase concentrations are generally higher than those of adult animals, seem more susceptible to rotavirus infections [4].
• The lag time for secretion of newly synthesized beta-galactosidase precursor was notably longer than that for the beta-glucuronidase precursor [7].

Chemical compound and disease context of Glb1

• GM1 gangliosidosis is a progressive neurodegenerative disease caused by deficiencies in lysosomal acid beta-galactosidase (beta-gal) and involves accumulation and storage of ganglioside GM1 and its asialo form (GA1) in brain and visceral tissues [8].

Biological context of Glb1

• Twitcher mice with an additional complete deficiency of acid beta-galactosidase have the mildest phenotype with the longest lifespan and nearly rescued CNS pathology [9].
• The WP5212 putative protein has high amino acid sequence homology with a wheat storage globulin, Glb1 [10].
• Substrate specificity and distribution of acid beta-galactosidase activities in seizure-susceptible and non-susceptible strains of mice [11].
• More likely, the Bgs region of chromosome 9 contains a gene cluster consisting of a number of regulatory and structural loci [12].
• Effects of double amino-acid substitution polymorphism in acid beta-galactosidase gene in two inbred strains of mice [13].

Anatomical context of Glb1

• Introduction of one polymorphism, Asn517-->Asp into the C57BL cDNA, did not alter the acid beta-galactosidase activity in the transfected COS-1 cells, while introduction of Gly539-->Arg completely abolished the catalytic activity [13].
• 3. Transfer and retention of 346J21 in breast cancer cell lines leads to growth arrest after 8-10 cell doublings, accompanied by the appearance of characteristic senescent cell morphology and senescence-associated acid beta-galactosidase activity [14].
• MIC cells co-cultured with 14-day intestinal endoderms promoted endodermal cell adhesion and growth, and the addition of exogeneous RA enhanced epithelial cell polarization and differentiation assessed by cytokeratin and lactase immunostaining [15].
• Correction of acid beta-galactosidase deficiency in GM1 gangliosidosis human fibroblasts by retrovirus vector-mediated gene transfer: higher efficiency of release and cross-correction by the murine enzyme [16].
• The predicted maximal lactase and alpha-glucosidase activities expressed by enterocytes migrating over Peyer's patch follicles were about one-quarter and one-half of values found in control villi [17].

Associations of Glb1 with chemical compounds

• A type 1 diabetes-related protein from wheat (Triticum aestivum). cDNA clone of a wheat storage globulin, Glb1, linked to islet damage [10].
• GM1-gangliosidosis is a progressive neurological disease in humans caused by deficiency of lysosomal acid beta-galactosidase, which hydrolyses the terminal beta-galactosidic residue from ganglioside GM1 and other glycoconjugates [18].
• The inhibition of mouse beta-galactosidase by the active-site-directed reagent N-bromoacetyl-beta-D-galactosylamine has been investigated. beta-Galactosidase from the high and low Bgs strains has identical affinity for this inhibitor [19].
• We measured the safety factor of the mouse intestinal brush-border hydrolase maltase in series with the glucose transporter SGLT1, for comparison with previous studies of sucrase and lactase [20].
• 2. Glucose-, fructose- and 3-O-methyl-glucose-containing diets increased sucrase and maltase but not lactase activities in mouse jejunal homogenates [21].

Other interactions of Glb1

• These observations are contrary to the expected outcome of Mendelian autosomal recessive single gene disorders and may also be interpreted as that the acid beta-galactosidase gene functions as a modifier gene for the phenotypic expression of genetic galactosylceramidase deficiency [9].
• The presence of the same beta-galactosidase bands in homogenates of rat kidney and small intestine as well as in neuraminidase-treated homogenates of liver and spleen suggests that the Glb-1 variants differ by one or more point mutations in the structural gene for "acid" beta-galactosidase [22].
• No significant linkage between Glb-1 and albino (LG I), brown (LG II), or hooded (LG VI) was observed [22].

Analytical, diagnostic and therapeutic context of Glb1

• Molecular cloning of mouse acid beta-galactosidase cDNA: sequence, expression of catalytic activity and comparison with the human enzyme [23].
• Studies of the response of p53-lacZ transgenic mice have uncovered an unexpected induction of endogenous acid-beta-galactosidase activity following whole body irradiation [24].
• This study suggests that lysosomal enzymes, contrary to the generalized perception in the field of gene therapy, may differ significantly in their properties and provides insights for design of future gene therapy interventions in acid beta-galactosidase deficiency [16].
• The results of two backcrosses and an intercross indicated that the isoelectric focusing phenotypes are controlled by two codominant alleles at a single autosomal locus, for which we propose the name Glb-1 [22].
• The induction of the synthesis of fucosyl asialo GM1 glycolipid, the expression of major histocompatibility complex class II molecule, an increase in the mitotic indices of colonic epithelial cells, and a decrease in lactase activity of the small intestinal epithelial cells also occurred only in the two groups [25].

References