Genomes and Genes
Gene Symbol: Gla
Description: galactosidase, alpha
Alias: Ags, alpha-galactosidase A, alpha-D-galactosidase A, alpha-D-galactoside galactohydrolase, melibiase
- Shu L, Shayman J. Caveolin-associated accumulation of globotriaosylceramide in the vascular endothelium of alpha-galactosidase A null mice. J Biol Chem. 2007;282:20960-7 pubmed
- Bodary P, Shen Y, Vargas F, Bi X, Ostenso K, Gu S, et al. Alpha-galactosidase A deficiency accelerates atherosclerosis in mice with apolipoprotein E deficiency. Circulation. 2005;111:629-32 pubmedAlpha-galactosidase A (Gla) deficiency leads to widespread tissue accumulation of neutral glycosphingolipids and is associated with premature vascular complications such as myocardial infarction and stroke...
- Yam G, Zuber C, Roth J. A synthetic chaperone corrects the trafficking defect and disease phenotype in a protein misfolding disorder. FASEB J. 2005;19:12-8 pubmed..Small molecule chemical chaperones will be therapeutically useful for various lysosomal storage disorders as well as for other genetic metabolic disorders caused by mutant but nonetheless catalytically active enzymes. ..
- Ohshima T, Murray G, Swaim W, Longenecker G, Quirk J, Cardarelli C, et al. alpha-Galactosidase A deficient mice: a model of Fabry disease. Proc Natl Acad Sci U S A. 1997;94:2540-4 pubmed
- Khanna R, Soska R, Lun Y, Feng J, Frascella M, Young B, et al. The pharmacological chaperone 1-deoxygalactonojirimycin reduces tissue globotriaosylceramide levels in a mouse model of Fabry disease. Mol Ther. 2010;18:23-33 pubmed publisher..Collectively, these data indicate that oral administration of DGJ increases mutant alpha-Gal A activity and reduces GL-3 in disease-relevant tissues in Tg/KO mice, and thus merits further evaluation as a treatment for Fabry disease. ..
- Park J, Whitesall S, D Alecy L, Shu L, Shayman J. Vascular dysfunction in the alpha-galactosidase A-knockout mouse is an endothelial cell-, plasma membrane-based defect. Clin Exp Pharmacol Physiol. 2008;35:1156-63 pubmed publisherFabry disease results from an X-linked mutation in the lysosomal alpha-galactosidase A (Gla) gene...
- Abe A, Gregory S, Lee L, Killen P, Brady R, Kulkarni A, et al. Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation. J Clin Invest. 2000;105:1563-71 pubmed..These data suggest that Fabry disease may be amenable to substrate deprivation therapy. ..
- Ohshima T, Murray G, Nagle J, Quirk J, Kraus M, Barton N, et al. Structural organization and expression of the mouse gene encoding alpha-galactosidase A. Gene. 1995;166:277-80 pubmed..Northern blot analysis revealed the widespread tissue distribution of mouse alpha GalA transcripts. Lower expression levels, however, were observed in some tissues, implying tissue-specific differences in alpha GalA promoter function. ..
- Eitzman D, Bodary P, Shen Y, Khairallah C, Wild S, Abe A, et al. Fabry disease in mice is associated with age-dependent susceptibility to vascular thrombosis. J Am Soc Nephrol. 2003;14:298-302 pubmedFabry disease is an X-linked lysosomal storage disorder due to deficiency of alpha-galactosidase A (GLA) activity that results in the widespread accumulation of neutral glycosphingolipids...
- Shu L, Park J, Byun J, Pennathur S, Kollmeyer J, Shayman J. Decreased nitric oxide bioavailability in a mouse model of Fabry disease. J Am Soc Nephrol. 2009;20:1975-85 pubmed publisher..These findings are consistent with a loss of NO bioavailability, associated with eNOS uncoupling, in the alpha-galactosidase A-knockout mouse. ..
- Darmoise A, Teneberg S, Bouzonville L, Brady R, Beck M, Kaufmann S, et al. Lysosomal alpha-galactosidase controls the generation of self lipid antigens for natural killer T cells. Immunity. 2010;33:216-28 pubmed publisher..Thus, we present TLR-dependent negative regulation of alpha-Gal-A as a mechanistic link between pathogen recognition and self lipid antigen induction for NKT cells. ..
- Adler D, West J, Chapman V. Expression of alpha-galactosidase in preimplantation mouse embryos. Nature. 1977;267:838-9 pubmed
- Oeltjen J, Malley T, Muzny D, Miller W, Gibbs R, Belmont J. Large-scale comparative sequence analysis of the human and murine Bruton's tyrosine kinase loci reveals conserved regulatory domains. Genome Res. 1997;7:315-29 pubmed..These data show the usefulness of large scale sequence comparisons to focus investigation on regions of noncoding sequence that play essential roles in complex gene regulation. ..
- Stephenson D, Grant S, Mullins L, Scolese A, O Reilly A, Chapman V. X-chromosome gene order in different Mus species crosses. Curr Top Microbiol Immunol. 1988;137:18-24 pubmed
- Shen J, Meng X, Wight Carter M, Day T, Goetsch S, Forni S, et al. Blocking hyperactive androgen receptor signaling ameliorates cardiac and renal hypertrophy in Fabry mice. Hum Mol Genet. 2015;24:3181-91 pubmed publisher..Our findings implicate abnormal AR pathway in the pathogenesis of Fabry disease and suggest blocking AR signaling as a novel therapeutic approach. ..
- Lusis A, West J. X-linked and autosomal genes controlling mouse alpha-galactosidase expression. Genetics. 1978;88:327-42 pubmedAnalysis of F2 and backcross animals has confirmed the X-chromosome linkage of Ags, the structural locus for mouse alpha-galactosidase...
- Hofmann L, Karl F, Sommer C, Uceyler N. Affective and cognitive behavior in the alpha-galactosidase A deficient mouse model of Fabry disease. PLoS ONE. 2017;12:e0180601 pubmed publisher..Our results indicate that genetic influences on affective and cognitive symptoms in FD may be of subordinate relevance, drawing attention to potential influences of environmental and epigenetic factors. ..
- Chamberlain J, Grant S, Reeves A, Mullins L, Stephenson D, Hoffman E, et al. Regional localization of the murine Duchenne muscular dystrophy gene on the mouse X chromosome. Somat Cell Mol Genet. 1987;13:671-8 pubmed..However, Southern analysis of portions of the mouse Dmd gene has not yet revealed any differences between mdx and wild-type mice. ..
- Lyu M, Kim W, Morse H, Kozak C. Genetic mapping in the mouse of Kif4, a gene encoding a kinesin-like motor protein. Mamm Genome. 1997;8:541 pubmed
- Ishii S, Yoshioka H, Mannen K, Kulkarni A, Fan J. Transgenic mouse expressing human mutant alpha-galactosidase A in an endogenous enzyme deficient background: a biochemical animal model for studying active-site specific chaperone therapy for Fabry disease. Biochim Biophys Acta. 2004;1690:250-7 pubmed..These TgM/KO mice and TMK cells are useful tools for studying the mechanism of ASSC therapy, and for screening ASSCs for Fabry disease. ..
- Hamanaka R, Shinohara T, Yano S, Nakamura M, Yasuda A, Yokoyama S, et al. Rescue of mutant alpha-galactosidase A in the endoplasmic reticulum by 1-deoxygalactonojirimycin leads to trafficking to lysosomes. Biochim Biophys Acta. 2008;1782:408-13 pubmed publisher..These data suggest that the rescue of R301Q from ERAD is a key step for normalization of intracellular trafficking of R301Q. ..
- Shen Y, Bodary P, Vargas F, Homeister J, Gordon D, Ostenso K, et al. Alpha-galactosidase A deficiency leads to increased tissue fibrin deposition and thrombosis in mice homozygous for the factor V Leiden mutation. Stroke. 2006;37:1106-8 pubmed..Fabry disease, an X-linked lysosomal storage disorder attributable to alpha-galactosidase A (GLA) deficiency, is associated with premature vascular events that may be thrombotic in nature...
- Itoh Y, Esaki T, Cook M, Qasba P, Shimoji K, Alroy J, et al. Local and global cerebral blood flow and glucose utilization in the alpha-galactosidase A knockout mouse model of Fabry disease. J Neurochem. 2001;79:1217-24 pubmed..These results indicate an impairment in cerebral energy metabolism in the Fabry mice, but one not necessarily due to circulatory insufficiency. ..
- Shiozuka C, Taguchi A, Matsuda J, Noguchi Y, Kunieda T, Uchio Yamada K, et al. Increased globotriaosylceramide levels in a transgenic mouse expressing human alpha1,4-galactosyltransferase and a mouse model for treating Fabry disease. J Biochem. 2011;149:161-70 pubmed publisher..These data indicated that the TgG3S(+/-) M(+/-)/KO mouse was suitable for studying ASSC therapy for Fabry disease, and that the TgG3S mouse would be useful for studying the effect of high Gb3 levels in mouse organs. ..
- Chapman V, Keitz B, Disteche C, Lau E, Snead M. Linkage of amelogenin (Amel) to the distal portion of the mouse X chromosome. Genomics. 1991;10:23-8 pubmed..The position of the amelogenin locus (Amel) relative to the loci for alpha-galactosidase (Ags), proteolipoprotein (Plp), and the random genomic probe DXWas31 has been determined...
- Higuchi K, Yoshimitsu M, Fan X, Guo X, Rasaiah V, Yen J, et al. Alpha-galactosidase A-Tat fusion enhances storage reduction in hearts and kidneys of Fabry mice. Mol Med. 2010;16:216-21 pubmed publisher..This strategy might advance not only gene therapy for Fabry disease and other LSDs, but also ERT, especially for cardiac Fabry disease. ..
- Oeltjen J, Liu X, Lu J, Allen R, Muzny D, Belmont J, et al. Sixty-nine kilobases of contiguous human genomic sequence containing the alpha-galactosidase A and Bruton's tyrosine kinase loci. Mamm Genome. 1995;6:334-8 pubmed..the genomic organization of the region surrounding btk and the Fabry disease gene, alpha-galactosidase A (gla), we constructed a 6-cosmid contig spanning the region from 5' of gla to 3' of btk...
- Herman G, Faust C, Darlison M, Barnard E. Genetic mapping of the mouse X chromosome in the region homologous to human Xq27-Xq28. Genomics. 1991;9:670-7 pubmed..Synteny with human Xq27-Xq28 is retained, although the relative order of some loci may differ between the two species. ..
- Ferraz M, Marques A, Appelman M, Verhoek M, Strijland A, Mirzaian M, et al. Lysosomal glycosphingolipid catabolism by acid ceramidase: formation of glycosphingoid bases during deficiency of glycosidases. FEBS Lett. 2016;590:716-25 pubmed publisher..The potential pathophysiological relevance of elevated glycosphingoid bases generated through this alternative metabolism in patients suffering from lysosomal glycosidase defects is discussed. ..
- Takahashi H, Hirai Y, Migita M, Seino Y, Fukuda Y, Sakuraba H, et al. Long-term systemic therapy of Fabry disease in a knockout mouse by adeno-associated virus-mediated muscle-directed gene transfer. Proc Natl Acad Sci U S A. 2002;99:13777-82 pubmed..AAV vector-mediated muscle-directed gene transfer provides an efficient and practical therapeutic approach for Fabry disease. ..
- Moore D, Gelderman M, Ferreira P, Fuhrmann S, Yi H, Elkahloun A, et al. Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach. Proc Natl Acad Sci U S A. 2007;104:8065-70 pubmed..These abnormalities form the basis for informed, in a Bayesian sense, sequential, hypothesis-driven research that can be subsequently tested experimentally. ..
- Nagamine C, Chan K, Kozak C, Lau Y. Chromosome mapping and expression of a putative testis-determining gene in mouse. Science. 1989;243:80-3 pubmed..0 kb) was mapped to chromosome 10. Hence, mYfin sequences have been duplicated several times in the mouse, although they are not duplicated in humans. ..
- Herman G, Walton S. Close linkage of the murine locus bare patches to the X-linked visual pigment gene: implications for mapping human X-linked dominant chondrodysplasia punctata. Genomics. 1990;7:307-12 pubmed..3-Xpter, where deletions associated with X-linked recessive chondrodysplasia punctata (CDPX) have been noted. This strategy should be applicable to the fine mapping of other dominant murine mutations. ..
- Disteche C, McConnell G, Grant S, Stephenson D, Chapman V, Gandy S, et al. Comparison of the physical and recombination maps of the mouse X chromosome. Genomics. 1989;5:177-84 pubmed..IX (Cf-8 and Cf-9), Duchenne muscular dystrophy (Dmd), phosphoglycerate kinase-1 (Pgk-1), and alpha-galactosidase (Ags), on the mouse X chromosome were determined by in situ hybridization...
- Lusis A, West J. X-linked inheritance of a structural gene for alpha-galactosidase in Mus musculus. Biochem Genet. 1976;14:849-55 pubmed
- Sasaki M, Takeda E, Takano K, Yomogida K, Katahira J, Yoneda Y. Molecular cloning and functional characterization of mouse Nxf family gene products. Genomics. 2005;85:641-53 pubmed..The orthologous relationship between human and mouse Nxf genes is discussed on the basis of these data. ..
- Gadola S, Silk J, Jeans A, Illarionov P, Salio M, Besra G, et al. Impaired selection of invariant natural killer T cells in diverse mouse models of glycosphingolipid lysosomal storage diseases. J Exp Med. 2006;203:2293-303 pubmed..These data suggest that GSL storage may result in alterations in thymic selection of iNKT cells caused by impaired presentation of selecting ligands. ..
- Yoshimitsu M, Higuchi K, Dawood F, Rasaiah V, Ayach B, Chen M, et al. Correction of cardiac abnormalities in fabry mice by direct intraventricular injection of a recombinant lentiviral vector that engineers expression of alpha-galactosidase A. Circ J. 2006;70:1503-8 pubmed..A localized benefit of directly injecting a therapeutic LV into the heart has been shown, confirming the utility of this delivery system for research and therapy for a variety of cardiovascular disorders. ..
- Shen J, Arning E, West M, Day T, Chen S, Meng X, et al. Tetrahydrobiopterin deficiency in the pathogenesis of Fabry disease. Hum Mol Genet. 2017;26:1182-1192 pubmed publisher..This study also suggested dissimilar efficacy of ERT and SRT in correcting pre-existing pathologies in Fabry disease. ..
- Shen Y, Luo B, Ou B, Chen A, Wang X, Li J. [Synergistic effect of deficiency in thrombosis-related genes]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2010;27:246-9 pubmed publisher..To generate mice carrying mutations in alpha-galactosidase A (Gla) and factor V Leiden (Fvl) and analyze the phenotypes, namely, tissue fibrin deposition and thrombus formation in ..
- Park S, Kim J, Joo K, Choi S, Choi E, Shin J, et al. Globotriaosylceramide leads to K(Ca)3.1 channel dysfunction: a new insight into endothelial dysfunction in Fabry disease. Cardiovasc Res. 2011;89:290-9 pubmed publisher..The animal model of Fabry disease, ?-galactosidase A (Gla) knockout mice, displayed age-dependent K(Ca)3.1 channel dysfunction. K(Ca)3...
- Mullins L, Grant S, Stephenson D, Chapman V. Multilocus molecular mapping of the mouse X chromosome. Genomics. 1988;3:187-94 pubmed..factor VIII), and Rsvp (red-sensitive visual pigment) and the known X-linked markers Otc, Hprt, Cf-9, G6pd, and Ags. From the centromere, the gene order was defined as Otc, Timp, Hprt, Cf-9, (Cf-8/Rsvp/G6pd), Ags, by minimizing the ..
- Tajima Y, Kawashima I, Tsukimura T, Sugawara K, Kuroda M, Suzuki T, et al. Use of a modified alpha-N-acetylgalactosaminidase in the development of enzyme replacement therapy for Fabry disease. Am J Hum Genet. 2009;85:569-80 pubmed publisherA modified alpha-N-acetylgalactosaminidase (NAGA) with alpha-galactosidase A (GLA)-like substrate specificity was designed on the basis of structural studies and was produced in Chinese hamster ovary cells...
- Francke U, Taggart R. Comparative gene mapping: order of loci on the X chromosome is different in mice and humans. Proc Natl Acad Sci U S A. 1980;77:3595-9 pubmed..that the breakpoint on the mouse X chromosome (in band XD) has separated the genes for HPRT (Hprt) and for GALA (Ags). Hprt is proximal to the breakpoint in region Xcen-XD and Ags is distal in region XD-Xter...
- Shen Y, He Z, Cai R, Pan J, Wang X, Li J. [Effect of alpha-galactosidase A deficiency on FV leiden fibrin deposition and thrombosis in mice]. Zhonghua Xue Ye Xue Za Zhi. 2009;30:162-5 pubmedTo evaluate the effect of alpha-galactosidase A (Gla) deficiency on FV Leiden (FVL) associated thrombosis in vivo. To generate the mice carrying mutations in Gla and FVL and analyze the tissue fibrin deposition in organs and thrombosis...
- Porubsky S, Speak A, Salio M, Jennemann R, Bonrouhi M, Zafarulla R, et al. Globosides but not isoglobosides can impact the development of invariant NKT cells and their interaction with dendritic cells. J Immunol. 2012;189:3007-17 pubmed publisher..Moreover, in ?GalA(-/-) mice, it is the Gb3 storage that is responsible for the decreased iNKT cell numbers and impeded Ag presentation on DCs. ..
- Chapman V, Kratzer P, Quarantillo B. Electrophoretic variation for X chromosome-linked hypoxanthine phosphoribosyl transferase (HPRT) in wild-derived mice. Genetics. 1983;103:785-95 pubmed..Linkage analysis involving the markers Pgk-1 and Ags indicated a gene order of centromere--Hprt--Pgk-1--Ags in crosses involving both stocks of wild mice.
- Uceyler N, Biko L, Hose D, Hofmann L, Sommer C. Comprehensive and differential long-term characterization of the alpha-galactosidase A deficient mouse model of Fabry disease focusing on the sensory system and pain development. Mol Pain. 2016;12: pubmed publisher..alpha-galactosidase A-deficient mice seem to model human Fabry disease and may be helpful when studying the pathophysiology of Fabry-associated pain. ..
- Amar L, Dandolo L, Hanauer A, Cook A, Arnaud D, Mandel J, et al. Conservation and reorganization of loci on the mammalian X chromosome: a molecular framework for the identification of homologous subchromosomal regions in man and mouse. Genomics. 1988;2:220-30 pubmed
- Pasteris N, de Gouyon B, Cadle A, Campbell K, Herman G, Gorski J. Cloning and regional localization of the mouse faciogenital dysplasia (Fgd1) gene. Mamm Genome. 1995;6:658-61 pubmed
- Nguyen Dinh Cat A, Escoubet B, Agrapart V, Griol Charhbili V, Schoeb T, Feng W, et al. Cardiomyopathy and response to enzyme replacement therapy in a male mouse model for Fabry disease. PLoS ONE. 2012;7:e33743 pubmed publisher..Enzyme replacement therapy affects cardiac molecular remodeling after a single dose. ..
- Noben Trauth K, Neely H, Brady R. Normal hearing in alpha-galactosidase A-deficient mice, the mouse model for Fabry disease. Hear Res. 2007;234:10-4 pubmed..disease (OMIM 301500) is a rare X-linked recessive disorder caused by mutations in the alpha-galactosidase gene (Gla)...
- Kang J, Shu L, Park J, Shayman J, Bodary P. Endothelial nitric oxide synthase uncoupling and microvascular dysfunction in the mesentery of mice deficient in ?-galactosidase A. Am J Physiol Gastrointest Liver Physiol. 2014;306:G140-6 pubmed publisherA defect in the gene for the lysosomal enzyme ?-galactosidase A (Gla) results in globotriaosylceramide (Gb3) accumulation in Fabry disease and leads to premature death from cardiac and cerebrovascular events...
- Bangari D, Ashe K, Desnick R, Maloney C, Lydon J, Piepenhagen P, et al. Î±-Galactosidase A knockout mice: progressive organ pathology resembles the type 2 later-onset phenotype of Fabry disease. Am J Pathol. 2015;185:651-65 pubmed publisher..Galactosidase A gene knockout (Gla KO) mice have no Î±-galactosidase A activity and progressively accumulate GL-3 in tissues and fluids, similarly ..
- Young Gqamana B, Brignol N, Chang H, Khanna R, Soska R, Fuller M, et al. Migalastat HCl reduces globotriaosylsphingosine (lyso-Gb3) in Fabry transgenic mice and in the plasma of Fabry patients. PLoS ONE. 2013;8:e57631 pubmed publisherFabry disease (FD) results from mutations in the gene (GLA) that encodes the lysosomal enzyme ?-galactosidase A (?-Gal A), and involves pathological accumulation of globotriaosylceramide (GL-3) and globotriaosylsphingosine (lyso-Gb3)...
- Gotlib R, Bishop D, Wang A, Zeidner K, Ioannou Y, Adler D, et al. The entire genomic sequence and cDNA expression of mouse alpha-galactosidase A. Biochem Mol Med. 1996;57:139-48 pubmed
- Francke U, Lalley P, Moss W, Ivy J, Minna J. Gene mapping in Mus musculus by interspecific cell hybridization: assignment of the genes for tripeptidase-1 to chromosome 10, dipeptidase-2 to chromosome 18, acid phosphatase-1 to chromosome 12, and adenylate kinase-1 to chromosome 2. Cytogenet Cell Genet. 1977;19:57-84 pubmed..Striking examples of norandom segregation of mouse chromosomes were observed in these hybrids with preferential retention of 15 and segregation of 11 and the Y chromosome. ..
- Taylor S, Osman N, McKenzie I, Sandrin M. Reduction of alpha-Gal expression by relocalizing alpha-galactosidase to the trans-Golgi network and cell surface. Glycobiology. 2002;12:729-39 pubmed..The ability to relocalize enzymes that modify cell surface carbohydrate structures has far-reaching implications in biology and may be useful in such fields as xenotransplantation and treatment of glycosidase disorders. ..
- Choi S, Kim J, Na H, Cho S, Park S, Jung S, et al. Globotriaosylceramide induces lysosomal degradation of endothelial KCa3.1 in fabry disease. Arterioscler Thromb Vasc Biol. 2014;34:81-9 pubmed publisher..Compared with MAECs from age-matched wild-type mice, those from aged ?-galactosidase A (Gla)-knockout mice, an animal model of FD, showed downregulated KCa3...
- Blewitt M, Gendrel A, Pang Z, Sparrow D, Whitelaw N, Craig J, et al. SmcHD1, containing a structural-maintenance-of-chromosomes hinge domain, has a critical role in X inactivation. Nat Genet. 2008;40:663-9 pubmed publisher..This finding links a group of proteins normally associated with structural aspects of chromosome biology with epigenetic gene silencing. ..
- Park J, Shu L, Shayman J. Differential involvement of COX1 and COX2 in the vasculopathy associated with the alpha-galactosidase A-knockout mouse. Am J Physiol Heart Circ Physiol. 2009;296:H1133-40 pubmed publisher..Defective lysosomal alpha-galactosidase A (Gla) is responsible for excessive Gb3 accumulation, and one cell sensitive to the effects of Gb3 accumulation is ..
- Macedo M, Quinta R, Pereira C, Sa Miranda M. Enzyme replacement therapy partially prevents invariant Natural Killer T cell deficiency in the Fabry disease mouse model. Mol Genet Metab. 2012;106:83-91 pubmed publisher..This study reveals that enzyme replacement therapy has a positive organ and subset-dependent effect in iNKT cells of Fabry knockout mice. ..
- Boskey A, Goldberg M, Kulkarni A, Gomez S. Infrared imaging microscopy of bone: illustrations from a mouse model of Fabry disease. Biochim Biophys Acta. 2006;1758:942-7 pubmed
- Mullins L, Stephenson D, Grant S, Chapman V. Efficient linkage of 10 loci in the proximal region of the mouse X chromosome. Genomics. 1990;7:19-30 pubmed..The possible significance of the Xlr loci is discussed with respect to other X-chromosome loci that regulate the immune response. ..