title: Generation and characterization of transgenic mice expressing a human mutant alpha-galactosidase with an R301Q substitution causing a variant form of Fabry disease.
abstract: Transgenic mice expressing a human mutant alpha-galactosidase with an R301Q substitution, which was found in a patient with a variant form of Fabry disease, were established. The mice transcribed a sufficient amount of alpha-galactosidase mRNA, but the steady-state levels of the enzyme protein were decreased in liver, kidney and heart, only residual activity being detected in these tissues. The mice will be useful for the clarification of the defective regulation of the structurally altered enzyme protein expressed by the mutant gene at the organ or individual level as well as for the evaluation of drugs that stabilize and/or activate the mutant alpha-galactosidase.
authors.affiliation: Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Science, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shimmoto
authors.forename: R
authors.initials: R
authors.lastname: Kase
authors.forename: K
authors.initials: K
authors.lastname: Itoh
authors.forename: K
authors.initials: K
authors.lastname: Utsumi
authors.forename: S
authors.initials: S
authors.lastname: Ishii
authors.forename: C
authors.initials: C
authors.lastname: Taya
authors.forename: H
authors.initials: H
authors.lastname: Yonekawa
authors.forename: H
authors.initials: H
authors.lastname: Sakuraba
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D000795:Fabry Disease / Q000201:enzymology / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D016296:Mutagenesis; D009206:Myocardium / Q000201:enzymology; D019076:Transgenes; D000519:alpha-Galactosidase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D000519:alpha-Galactosidase