This report describes mucopolysaccharidosis type VII (MPS7); MPS7 exhibits autosomal recessive inheritance. The human gene implicated in this disease is GUSB (glucuronidase beta) a hydrolase that degrades glycosaminoglycans (mucopolysaccharides). There are two orthologous genes in Drosophila, βGlu and CG15117, for which RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated. For Dmel\βGlu, an amorphic allele generated by targeted recombination has also been generated.
The human GUSB gene has not been introduced into flies.
The Dmel\βGlu has been studied in the context of the disease model. Animals homozygous for an amorphic allele of βGlu exhibit reduced lifespan, progressive locomotor defects, neuropathological abnormalities including loss of dopaminergic neurons in the brain, and muscle degeneration. Therapeutic administration of resveratrol ameliorates most of the neurological, muscular, and locomotor phenotypes.
The CG15117 gene contributes a low level of glucuronidase activity in animals that are null for the βGlu gene. The enzyme encoded by CG15117 lacks the N-terminal ER-targeting signal peptide, suggesting it is not localized to the lysosome; it has been shown to be approximately 6-fold less active the Dmel\βGlu.
[updated Mar. 2019 by FlyBase; FBrf0222196]
Lysosomal storage disease that involves the accumulation of glycosaminoglycans in the tissues and their excretion in the urine (DOID:12798)
The mucopolysaccharidoses are a group of inherited disorders caused by a lack of specific lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs), or mucopolysaccharides. The accumulation of partially degraded GAGs causes interference with cell, tissue, and organ function. [from MIM:607014; 2018.07.20]
[MUCOPOLYSACCHARIDOSIS, TYPE VII; MPS7](https://omim.org/entry/253220)
[BETA-GLUCURONIDASE; GUSB](https://omim.org/entry/611499)
Mucopolysaccharidosis type VII is an autosomal recessive lysosomal storage disease characterized by the inability to degrade glucuronic acid-containing glycosaminoglycans. The phenotype is highly variable, ranging from severe lethal hydrops fetalis to mild forms with survival into adulthood. Most patients with the intermediate phenotype show hepatomegaly, skeletal anomalies, coarse facies, and variable degrees of mental impairment (Shipley et al., 1993; pubmed:7680524). [from MIM:253220; 2019.03.20]
Mucopolysaccharidosis type VII (MPS7) is caused by homozygous or compound heterozygous mutation in the gene encoding beta-glucuronidase (GUSB). [from MIM:253220; 2019.03.20]
GUSB encodes Glucuronidase Beta, a hydrolase that degrades glycosaminoglycans, including heparan sulfate, dermatan sulfate, and chondroitin-4,6-sulfate. The enzyme forms a homotetramer that is localized to the lysosome. [Gene Cards, GUSB; 2019.03.20]
One to many: 1 human to 2 Drosophila.
High-scoring ortholog of human GUSB (2 Drosophila to 1 human). Dmel\βGlu shares 43% identity and 62% similarity with the human gene.
